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Entry
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- #260350 - PANCREATIC CANCER
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- OMIM
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<p>
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<span class="h4">#260350</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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</li>
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<li role="presentation">
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<a href="/clinicalSynopsis/260350"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#history">History</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div id="mimFloatingLinksMenu">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=PANCREATIC CANCER" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=3708&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/5551" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/kras" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=260350[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1333" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:4905" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/260350" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://omia.org/OMIA001990/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:4905" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 372142002<br />
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<strong>ORPHA:</strong> 1333<br />
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<strong>DO:</strong> 4905<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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260350
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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PANCREATIC CANCER
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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PANCREATIC CARCINOMA<br />
|
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PANCREATIC ACINAR CARCINOMA
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/12/240?start=-3&limit=10&highlight=240">
|
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12p12.1
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Pancreatic carcinoma, somatic
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
<a href="/entry/260350"> 260350 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
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</span>
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|
</td>
|
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<td>
|
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<span class="mim-font">
|
|
KRAS
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/190070"> 190070 </a>
|
|
</span>
|
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</td>
|
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</tr>
|
|
|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/12/394?start=-3&limit=10&highlight=394">
|
|
12q13.13
|
|
</a>
|
|
</span>
|
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</td>
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<td>
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<span class="mim-font">
|
|
Pancreatic cancer, somatic
|
|
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/260350"> 260350 </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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</span>
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</td>
|
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<td>
|
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<span class="mim-font">
|
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ACVR1B
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/601300"> 601300 </a>
|
|
</span>
|
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</td>
|
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</tr>
|
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|
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/17/175?start=-3&limit=10&highlight=175">
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17p13.1
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Pancreatic cancer, somatic
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/260350"> 260350 </a>
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
TP53
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/191170"> 191170 </a>
|
|
</span>
|
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</td>
|
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</tr>
|
|
|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/18/189?start=-3&limit=10&highlight=189">
|
|
18q21.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Pancreatic cancer, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/260350"> 260350 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
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</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
SMAD4
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600993"> 600993 </a>
|
|
</span>
|
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</td>
|
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</tr>
|
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|
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/19/46?start=-3&limit=10&highlight=46">
|
|
19p13.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Pancreatic cancer, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/260350"> 260350 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
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</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
STK11
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/602216"> 602216 </a>
|
|
</span>
|
|
</td>
|
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</tr>
|
|
|
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</tbody>
|
|
</table>
|
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</div>
|
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</div>
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<div>
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|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/260350" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
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|
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/260350" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/260350" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br /> -
|
|
Somatic mutation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/124975008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">124975008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866227&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866227</a>, <a href="https://bioportal.bioontology.org/search?q=C0544886&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0544886</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001442</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001442</a>]</span><br /> -
|
|
Multifactorial <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837655&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837655</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Pancreas </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Pancreatic cancer <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/372142002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">372142002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/363418001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">363418001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C25" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C25</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/C25.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C25.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/157.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">157.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/157" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">157</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235974&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235974</a>, <a href="https://bioportal.bioontology.org/search?q=C0346647&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0346647</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002894" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002894</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002894" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002894</a>]</span><br /> -
|
|
Pancreatic ductal adenocarcinoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/792907004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">792907004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1335302&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1335302</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEOPLASIA </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Pancreatic ductal adenocarcinoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/792907004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">792907004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1335302&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1335302</a>]</span><br />
|
|
|
|
</span>
|
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</div>
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</div>
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</div>
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- May be seen with other forms of cancer in a family<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Susceptibility conferred by somatic mutation in Kirsten rat sarcoma-2 viral (v-Ki-ras2) oncogene homolog gene (KRAS, <a href="/entry/190070#0005">190070.0005</a>)<br /> -
|
|
Susceptibility conferred by somatic mutation in the tumor protein 53 gene (TP53, <a href="/entry/191170#0027">191170.0027</a>)<br /> -
|
|
Susceptibility conferred by somatic mutation in the mothers against decapentaplegic, Drosophila, homolog of, 4 gene (MADH4, <a href="/entry/600993#0001">600993.0001</a>)<br /> -
|
|
Susceptibility conferred by somatic mutation in the serine/threonine protein kinase 11 gene (STK11, <a href="/entry/602216#0015">602216.0015</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
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</div>
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</div>
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<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
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</div>
|
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</div>
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</div>
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<div>
|
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<br />
|
|
</div>
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<div>
|
|
<a id="text" class="mim-anchor"></a>
|
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|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
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<p>A number sign (#) is used with this entry because mutations in a number of genes are associated with pancreatic carcinoma, familial or sporadic, germline or somatic.</p>
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<p>Pancreatic cancer shows among the highest mortality rates of any cancer, with a 5-year relative survival rate of less than 5%. By the time of initial diagnosis, metastatic disease is commonly present. Established risk factors include a family history of pancreatic cancer, a medical history of diabetes type 2, and cigarette smoking (summary by <a href="#3" class="mim-tip-reference" title="Amundadottir, L., Kraft, P., Stolzenberg-Solomon, R. Z., Fuchs, C. S., Petersen, G. M., Arslan, A. A., Bueno-de-Mesquita, H. B., Gross, M., Helzlsouer, K., Jacobs, E. J., LaCroix, A., Zheng, W., and 59 others. <strong>Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.</strong> Nature Genet. 41: 986-990, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19648918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19648918</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19648918[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19648918">Amundadottir et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19648918" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Genetic Heterogeneity of Pancreatic Cancer</em></strong></p><p>
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Somatic mutations in pancreatic cancer occur in the KRAS (<a href="/entry/190070">190070</a>), CDKN2A (<a href="/entry/600160">600160</a>), MADH4 (<a href="/entry/600993">600993</a>), TP53 (<a href="/entry/191170">191170</a>), ARMET (<a href="/entry/601916">601916</a>), STK11 (<a href="/entry/602216">602216</a>), ACVR1B (<a href="/entry/601300">601300</a>), and RBBP8 (<a href="/entry/604124">604124</a>) genes.</p><p>Susceptibility loci for pancreatic cancer include PNCA1 (<a href="/entry/606856">606856</a>), related to mutation in the PALLD gene on chromosome 4q32 (<a href="/entry/608092">608092</a>); PNCA2 (<a href="/entry/613347">613347</a>), related to mutation in the BRCA2 gene on chromosome 13q12 (<a href="/entry/600185">600185</a>); PNCA3 (<a href="/entry/613348">613348</a>), related to mutation in the PALB2 gene on chromosome 16p12 (<a href="/entry/610355">610355</a>); PNCA4 (<a href="/entry/614320">614320</a>), related to mutation in the BRCA1 gene on chromosome 17q21 (<a href="/entry/113705">113705</a>); and PNCA5 (<a href="/entry/618680">618680</a>), related to mutation in the RABL3 gene on chromosome 3q13 (<a href="/entry/618542">618542</a>).</p><p><strong><em>Occurrence of Pancreatic Cancer in Other Disorders</em></strong></p><p>
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Several familial cancer syndromes increase the risk of pancreatic cancer. The best characterized include hereditary nonpolyposis colon cancer syndrome (HNPCC; see <a href="/entry/120435">120435</a>); hereditary breast-ovarian cancer syndrome due to mutations in BRCA2; Peutz-Jeghers syndrome (<a href="/entry/175200">175200</a>); the melanoma-pancreatic cancer syndrome (<a href="/entry/606719">606719</a>), caused by mutations in CDKN2A (<a href="/entry/600160">600160</a>); von Hippel-Lindau syndrome (<a href="/entry/193300">193300</a>), ataxia-telangiectasia (<a href="/entry/208900">208900</a>) (<a href="#41" class="mim-tip-reference" title="Swift, M., Sholman, L., Perry, M., Chase, C. <strong>Malignant neoplasms in the families of patients with ataxia-telangiectasia.</strong> Cancer Res. 36: 209-215, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1248000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1248000</a>]" pmid="1248000">Swift et al., 1976</a>), and juvenile polyposis syndrome (<a href="/entry/174900">174900</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1248000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Patients with hereditary pancreatitis (<a href="/entry/167800">167800</a>) resulting from gain-of-function mutations in the protease serine-1 gene (PRSS1; <a href="/entry/276000">276000</a>) have a lifetime pancreatic cancer risk ratio of 57 and a cumulative incidence, to age 70 years, of 40% (<a href="#27" class="mim-tip-reference" title="Lowenfels, A. B., Maisonneuve, P., DiMagno, E. P., Elitsur, Y., Gates, L. K., Jr., Perrault, J., Whitcomb, D. C., The International Hereditary Pancreatitis Study Group. <strong>Hereditary pancreatitis and the risk of pancreatic cancer.</strong> J. Nat. Cancer Inst. 89: 442-446, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9091646/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9091646</a>] [<a href="https://doi.org/10.1093/jnci/89.6.442" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9091646">Lowenfels et al., 1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9091646" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#18" class="mim-tip-reference" title="Friedman, J. M., Fialkow, P. J. <strong>Familial carcinoma of the pancreas.</strong> Clin. Genet. 9: 463-469, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1269168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1269168</a>] [<a href="https://doi.org/10.1111/j.1399-0004.1976.tb01598.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1269168">Friedman and Fialkow (1976)</a> observed cancer of the pancreas in 4 brothers from a sibship of 6. Diagnosis was made between ages 66 and 75 years. None had a history of pancreatitis or tumors at other sites. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1269168" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Reimer, R. R., Fraumeni, J. F., Jr., Ozols, R. F., Bender, R. <strong>Pancreatic cancer in father and son. (Letter)</strong> Lancet 309: 911 only, 1977. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/67325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">67325</a>] [<a href="https://doi.org/10.1016/s0140-6736(77)91244-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="67325">Reimer et al. (1977)</a> reported pancreatic cancer in father and son. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=67325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a family of European Jewish ancestry, <a href="#15" class="mim-tip-reference" title="Ehrenthal, D., Haeger, L., Griffin, T., Compton, C. <strong>Familial pancreatic adenocarcinoma in three generations: a case report and a review of the literature.</strong> Cancer 59: 1661-1664, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3828965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3828965</a>] [<a href="https://doi.org/10.1002/1097-0142(19870501)59:9<1661::aid-cncr2820590923>3.0.co;2-h" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3828965">Ehrenthal et al. (1987)</a> identified pancreatic adenocarcinoma in women of 3 successive generations. The diagnosis was histologically confirmed in each case. The youngest of the 3 women presented at age 29, her mother at age 42, and her grandmother at age 76. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3828965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Lynch, H. T., Fusaro,L., Smyrk, T. C., Watson, P., Lanspa, S., Lynch, J. F. <strong>Medical genetic study of eight pancreatic cancer-prone families.</strong> Cancer Invest. 13: 141-149, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7874567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7874567</a>] [<a href="https://doi.org/10.3109/07357909509011683" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7874567">Lynch et al. (1995)</a> studied 8 families in which 2 or more first-degree relatives had pancreatic cancer. In the 8 families, 25 pancreatic cancers were found. The mean age of occurrence was 62.8 years, with a range from 45 to 90 years. Parent and child occurrence was observed in 4 of the 8 families. In one family, the progenitor had an affected brother and 5 of his 8 children developed cancer; 2 had pancreatic cancer, 2 had breast cancer (one of these also had pancreatic cancer), and 1 daughter had ovarian cancer. Of the 7 carcinomas available for pathologic review, 6 were typical ductal adenocarcinomas and the seventh was a giant cell variant of ductal carcinoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7874567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Caldas, C., Hahn, S. A., da Costa, L. T., Redston, M. S., Schutte, M., Seymour, A. B., Weinstein, C. L., Hruban, R. H., Yeo, C. J., Kern, S. E. <strong>Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma.</strong> Nature Genet. 8: 27-32, 1994. Note: Erratum: Nature Genet. 8: 410 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726912</a>] [<a href="https://doi.org/10.1038/ng0994-27" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7726912">Caldas et al. (1994)</a> quoted <a href="#11" class="mim-tip-reference" title="Boring, C. C., Squires, T. S., Tong, T. <strong>Cancer statistics, 1993.</strong> CA Cancer J. Clin. 43: 7-26, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8422609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8422609</a>] [<a href="https://doi.org/10.3322/canjclin.43.1.7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8422609">Boring et al. (1993)</a> as indicating that pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death in either sex in the United States, with an estimated incidence in 1993 of nearly 27,700 and a mortality of 24,500. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8422609+7726912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Evans, J. P., Burke, W., Chen, R., Bennett, R. L., Schmidt, R. A., Patchen Dellinger, E., Kimmey, M., Crispin, D., Brentnall, T. A., Byrd, D. R. <strong>Familial pancreatic adenocarcinoma: association with diabetes and early molecular diagnosis.</strong> J. Med. Genet. 32: 330-335, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7616537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7616537</a>] [<a href="https://doi.org/10.1136/jmg.32.5.330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7616537">Evans et al. (1995)</a> described a large pedigree in which pancreatic cancer was inherited as an autosomal dominant. Diabetes and exocrine insufficiency were observed in all family members who eventually developed pancreatic cancer. The presence of diabetes, often years before the diagnosis of cancer, allowed identification of those people who had inherited the predisposing allele. The lack of attacks of abdominal pain seemingly distinguishes the affected members of this family from hereditary pancreatitis (<a href="/entry/167800">167800</a>) in which diabetes mellitus and pancreatic cancer occur, but the distinction is by no means clear because it was stated that 6 of the 9 persons who developed pancreatic cancer in this family also had a history clinically compatible with pancreatic insufficiency before diagnosis of cancer: weight loss, fatty and foul smelling stools, increased fecal fat, and relief with exogenous pancreatic enzyme supplementation. All 9 members of the family with pancreatic cancer were males. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7616537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Making use of pathologic, clinical, and genetic knowledge, <a href="#21" class="mim-tip-reference" title="Hruban, R. H., Goggins, M., Parsons, J., Kern, S. E. <strong>Progression model for pancreatic cancer.</strong> Clin. Cancer Res. 6: 2969-2972, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10955772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10955772</a>]" pmid="10955772">Hruban et al. (2000)</a> composed a progression model of pancreatic carcinoma, similar to that developed for colorectal carcinoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10955772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Because CD40 (<a href="/entry/109535">109535</a>) activation can reverse immune suppression and drive antitumor T cell responses, <a href="#8" class="mim-tip-reference" title="Beatty, G. L., Chiorean, E. G., Fishman, M. P., Saboury, B., Teitelbaum, U. R., Sun, W., Huhn, R. D., Song, W., Li, D., Sharp, L. L., Torigian, D. A., O'Dwyer, P. J., Vonderheide, R. H. <strong>CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans.</strong> Science 331: 1612-1616, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21436454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21436454</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21436454[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1198443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21436454">Beatty et al. (2011)</a> tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable pancreatic ductal adenocarcinoma (PDA) and observed tumor regressions in some patients. They reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, <a href="#8" class="mim-tip-reference" title="Beatty, G. L., Chiorean, E. G., Fishman, M. P., Saboury, B., Teitelbaum, U. R., Sun, W., Huhn, R. D., Song, W., Li, D., Sharp, L. L., Torigian, D. A., O'Dwyer, P. J., Vonderheide, R. H. <strong>CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans.</strong> Science 331: 1612-1616, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21436454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21436454</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21436454[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1198443" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21436454">Beatty et al. (2011)</a> concluded that cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, their findings demonstrated a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21436454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of SMAD4 (<a href="/entry/600993">600993</a>). As loss of neighboring housekeeping genes can confer collateral lethality, <a href="#14" class="mim-tip-reference" title="Dey, P., Baddour, J., Muller, F., Wu, C. C., Wang, H., Liao, W.-T., Lan, Z., Chen, A., Gutschner, T., Kang, Y., Fleming, J., Satani, N., and 13 others. <strong>Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer.</strong> Nature 542: 119-123, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28099419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28099419</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28099419[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature21052" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28099419">Dey et al. (2017)</a> sought to determine whether loss of the metabolic gene malic enzyme-2 (ME2; <a href="/entry/154270">154270</a>) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3 (<a href="/entry/604626">604626</a>). <a href="#14" class="mim-tip-reference" title="Dey, P., Baddour, J., Muller, F., Wu, C. C., Wang, H., Liao, W.-T., Lan, Z., Chen, A., Gutschner, T., Kang, Y., Fleming, J., Satani, N., and 13 others. <strong>Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer.</strong> Nature 542: 119-123, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28099419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28099419</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28099419[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature21052" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28099419">Dey et al. (2017)</a> showed that ME3 depletion selectively kills ME2-null PDAC cells in a manner consistent with an essential function for ME3 in ME2-null cancer cells. Mechanistically, integrated metabolomic and molecular investigation of cells deficient in mitochondrial malic enzymes revealed diminished NADPH production and consequent high levels of reactive oxygen species. These changes activate AMP-activated protein kinase (AMPK; see <a href="/entry/602739">602739</a>), which in turn directly suppresses sterol regulatory element-binding protein-1 (SREBP1; <a href="/entry/184756">184756</a>)-directed transcription of its direct targets, including the branched-chain amino acid transaminase-2 gene BCAT2 (<a href="/entry/113530">113530</a>). BCAT2 catalyses the transfer of the amino group from branched-chain amino acids to alpha-ketoglutarate, thereby regenerating glutamate, which functions in part to support de novo nucleotide synthesis. Thus, mitochondrial malic enzyme deficiency, which results in impaired NADPH production, provides a prime 'collateral lethality' therapeutic strategy for the treatment of a substantial fraction of patients diagnosed with intractable pancreatic cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28099419" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Starting with a systematic proteomic investigation of secreted pancreatic cancer disease mediators and underlying molecular mechanisms, <a href="#39" class="mim-tip-reference" title="Shi, Y., Gao, W., Lytle, N. K., Huang, P., Yuan, X., Dann, A. M., Ridinger-Saison, M., DelGiorno, K. E., Antal, C. E., Liang, G., Atkins, A. R., Erikson, G., and 25 others. <strong>Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.</strong> Nature 569: 131-135, 2019. Note: Erratum: Nature 600: E18, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30996350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30996350</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30996350[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-019-1130-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30996350">Shi et al. (2019)</a> revealed that leukemia inhibitory factor (LIF; <a href="/entry/159540">159540</a>) is a key paracrine factor from activated pancreatic stellate cells acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifr deletion markedly slowed tumor progression and augmented the efficacy of chemotherapy to prolong survival of pancreatic ductal adenocarcinoma mouse models, mainly by modulating cancer cell differentiation and epithelial-mesenchymal transition status. Moreover, in both mouse models and human pancreatic ductal adenocarcinoma, aberrant production of LIF in the pancreas was restricted to pathologic conditions and correlated with pancreatic ductal adenocarcinoma pathogenesis, and changes in the levels of circulating LIF correlated well with tumor response to therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30996350" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Banke, M. G., Mulvihill, J. J., Aston, C. E. <strong>Inheritance of pancreatic cancer in pancreatic cancer-prone families.</strong> Med. Clin. North Am. 84: 677-690, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10872424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10872424</a>] [<a href="https://doi.org/10.1016/s0025-7125(05)70250-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10872424">Banke et al. (2000)</a> estimated that 10% or more of patients with pancreatic cancer inherit the risk in an autosomal dominant pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10872424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#30" class="mim-tip-reference" title="McWilliams, R. R., Rabe, K. G., Olswold, C., De Andrade, M., Petersen, G. M. <strong>Risk of malignancy in first-degree relatives of patients with pancreatic carcinoma.</strong> Cancer 104: 388-394, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15912495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15912495</a>] [<a href="https://doi.org/10.1002/cncr.21166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15912495">McWilliams et al. (2005)</a> analyzed family history questionnaires from 426 patients with pancreatic cancer and compared the prevalence of malignancy reported in 3,355 of their first-degree relatives to population data from the Surveillance, Epidemiology, and End Results (SEER) Project, using age- and gender-adjusted incidence rates. <a href="#30" class="mim-tip-reference" title="McWilliams, R. R., Rabe, K. G., Olswold, C., De Andrade, M., Petersen, G. M. <strong>Risk of malignancy in first-degree relatives of patients with pancreatic carcinoma.</strong> Cancer 104: 388-394, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15912495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15912495</a>] [<a href="https://doi.org/10.1002/cncr.21166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15912495">McWilliams et al. (2005)</a> found an increased risk of pancreatic and liver carcinoma in the first-degree relatives of probands with pancreatic cancer (1.88- and 2.7-fold, respectively); the risk for pancreatic cancer was nearly 3-fold when the proband was diagnosed before 60 years of age, but no other malignancies were increased in this subgroup. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15912495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Berman, D. M., Karhadkar, S. S., Maitra, A., Montes de Oca, R., Gerstenblith, M. R., Briggs, K., Parker, A. R., Shimada, Y., Eshleman, J. R., Watkins, D. N., Beachy, P. A. <strong>Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours.</strong> Nature 425: 846-851, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520411</a>] [<a href="https://doi.org/10.1038/nature01972" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520411">Berman et al. (2003)</a> demonstrated that a wide range of digestive tract tumors, including most of those originating in the esophagus, stomach, biliary tract, and pancreas, but not in the colon, display increased hedgehog pathway activity, which is suppressible by cyclopamine, a hedgehog pathway antagonist. Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumors in vivo. Unlike tumors in Gorlin syndrome (<a href="/entry/109400">109400</a>), pathway activity and cell growth in these digestive tract tumors are driven by endogenous expression of hedgehog ligands, as indicated by the presence of Sonic hedgehog (SHH; <a href="/entry/600725">600725</a>) and Indian hedgehog (IHH; <a href="/entry/600726">600726</a>) transcripts, by the pathway- and growth-inhibitory activity of a hedgehog-neutralizing antibody, and by the dramatic growth-stimulatory activity of exogenously added hedgehog ligand. <a href="#9" class="mim-tip-reference" title="Berman, D. M., Karhadkar, S. S., Maitra, A., Montes de Oca, R., Gerstenblith, M. R., Briggs, K., Parker, A. R., Shimada, Y., Eshleman, J. R., Watkins, D. N., Beachy, P. A. <strong>Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours.</strong> Nature 425: 846-851, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520411</a>] [<a href="https://doi.org/10.1038/nature01972" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520411">Berman et al. (2003)</a> concluded that their results identified a group of common lethal malignancies in which hedgehog pathway activity, essential for tumor growth, is activated not by mutation but by ligand expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#42" class="mim-tip-reference" title="Thayer, S. P., di Magliano, M. P., Heiser, P. W., Nielsen, C. M., Roberts, D. J., Lauwers, G. Y., Qi, Y. P., Gysin, S., Fernandez-del Castillo, C., Yajnik, V., Antoniu, B., McMahon, M., Warshaw, A. L., Hebrok, M. <strong>Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis.</strong> Nature 425: 851-856, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520413</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14520413[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature02009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520413">Thayer et al. (2003)</a> reported that Sonic hedgehog is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions, pancreatic intraepithelial neoplasia. The pancreata of Pdx1- (<a href="/entry/600733">600733</a>) Shh mice (in which Sonic hedgehog is misexpressed in the pancreatic endoderm) developed abnormal tubular structures, a phenocopy of human pancreatic intraepithelial neoplasia-1 and -2. Moreover, these pancreatic intraepithelial neoplasia-like lesions also contained mutations in Kras (<a href="/entry/190070">190070</a>) and overexpressed Erbb2 (<a href="/entry/164870">164870</a>), which are genetic mutations found early in the progression of human pancreatic cancer. Furthermore, hedgehog signaling remained active in cell lines established from primary and metastatic pancreatic adenocarcinomas. Notably, inhibition of hedgehog signaling by cyclopamine induced apoptosis and blocked proliferation in a subset of the pancreatic cancer cell lines both in vitro and in vivo. <a href="#42" class="mim-tip-reference" title="Thayer, S. P., di Magliano, M. P., Heiser, P. W., Nielsen, C. M., Roberts, D. J., Lauwers, G. Y., Qi, Y. P., Gysin, S., Fernandez-del Castillo, C., Yajnik, V., Antoniu, B., McMahon, M., Warshaw, A. L., Hebrok, M. <strong>Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis.</strong> Nature 425: 851-856, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520413</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14520413[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature02009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14520413">Thayer et al. (2003)</a> concluded that their data suggested that the hedgehog pathway may have an early and critical role in the genesis of pancreatic cancer, and that maintenance of hedgehog signaling is important for aberrant proliferation and tumorigenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520413" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., Hong, S.-M., Fu, B., and 24 others. <strong>Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.</strong> Science 321: 1801-1806, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18772397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18772397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18772397[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1164368" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18772397">Jones et al. (2008)</a> performed a comprehensive genetic analysis of 24 pancreatic cancers. They determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. They then searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for approximately 1 million SNPs. <a href="#24" class="mim-tip-reference" title="Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., Hong, S.-M., Fu, B., and 24 others. <strong>Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.</strong> Science 321: 1801-1806, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18772397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18772397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18772397[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1164368" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18772397">Jones et al. (2008)</a> found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors. Analysis of these tumors' transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the importance of these pathways and processes. <a href="#24" class="mim-tip-reference" title="Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., Hong, S.-M., Fu, B., and 24 others. <strong>Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.</strong> Science 321: 1801-1806, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18772397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18772397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18772397[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1164368" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18772397">Jones et al. (2008)</a> concluded that genetically altered core pathways and regulatory processes only become evident once the coding regions of the genome are analyzed in depth. The authors suggested that dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis. The 12 signaling pathways implicated in pancreatic tumorigenesis included apoptosis, DNA damage control, regulation of the G1/S phase transition, hedgehog signaling, homophilic cell adhesion, integrin signaling, C-Jun (<a href="/entry/165160">165160</a>) N-terminal kinase signaling, KRAS (<a href="/entry/190070">190070</a>) signaling, regulation of invasion, small GTPase-dependent signaling other than KRAS, TGF-beta (<a href="/entry/190180">190180</a>) signaling, and WNT (see <a href="/entry/164975">164975</a>)/Notch (<a href="/entry/190198">190198</a>) signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18772397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Campbell, P. J., Yachida, S., Mudie, L. J., Stephens, P. J., Pleasance, E. D., Stebbings, L. A., Morsberger, L. A., Latimer, C., McLaren, S., Lin, M.-L., McBride, D. J., Varela, I., and 13 others. <strong>The patterns and dynamics of genomic instability in metastatic pancreatic cancer.</strong> Nature 467: 1109-1113, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20981101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20981101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20981101[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20981101">Campbell et al. (2010)</a> used advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. <a href="#13" class="mim-tip-reference" title="Campbell, P. J., Yachida, S., Mudie, L. J., Stephens, P. J., Pleasance, E. D., Stebbings, L. A., Morsberger, L. A., Latimer, C., McLaren, S., Lin, M.-L., McBride, D. J., Varela, I., and 13 others. <strong>The patterns and dynamics of genomic instability in metastatic pancreatic cancer.</strong> Nature 467: 1109-1113, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20981101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20981101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20981101[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20981101">Campbell et al. (2010)</a> found that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, i.e., dysregulated G1-to-S-phase transition with intact G2-M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing parallel and even convergent evolution among different metastases. <a href="#13" class="mim-tip-reference" title="Campbell, P. J., Yachida, S., Mudie, L. J., Stephens, P. J., Pleasance, E. D., Stebbings, L. A., Morsberger, L. A., Latimer, C., McLaren, S., Lin, M.-L., McBride, D. J., Varela, I., and 13 others. <strong>The patterns and dynamics of genomic instability in metastatic pancreatic cancer.</strong> Nature 467: 1109-1113, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20981101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20981101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20981101[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20981101">Campbell et al. (2010)</a> found evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumors, and that phylogenetic trees across metastases show organ-specific branches. <a href="#13" class="mim-tip-reference" title="Campbell, P. J., Yachida, S., Mudie, L. J., Stephens, P. J., Pleasance, E. D., Stebbings, L. A., Morsberger, L. A., Latimer, C., McLaren, S., Lin, M.-L., McBride, D. J., Varela, I., and 13 others. <strong>The patterns and dynamics of genomic instability in metastatic pancreatic cancer.</strong> Nature 467: 1109-1113, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20981101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20981101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20981101[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09460" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20981101">Campbell et al. (2010)</a> concluded that their data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20981101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#45" class="mim-tip-reference" title="Yachida, S., Jones, S., Bozic, I., Antal, T., Leary, R., Fu, B., Kamiyama, M., Hruban, R. H., Eshleman, J. R., Nowak, M. A., Velculescu, V. E., Kinzler, K. W., Vogelstein, B., Iacobuzio-Donahue, C. A. <strong>Distant metastasis occurs late during the genetic evolution of pancreatic cancer.</strong> Nature 467: 1114-1117, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20981102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20981102</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20981102[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09515" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20981102">Yachida et al. (2010)</a> used data generated by sequencing the genomes of 7 pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers and found that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, nonmetastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, nonmetastatic founder cell. At least 5 more years are required for the acquisition of metastatic ability, and patients die an average of 2 years thereafter. <a href="#45" class="mim-tip-reference" title="Yachida, S., Jones, S., Bozic, I., Antal, T., Leary, R., Fu, B., Kamiyama, M., Hruban, R. H., Eshleman, J. R., Nowak, M. A., Velculescu, V. E., Kinzler, K. W., Vogelstein, B., Iacobuzio-Donahue, C. A. <strong>Distant metastasis occurs late during the genetic evolution of pancreatic cancer.</strong> Nature 467: 1114-1117, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20981102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20981102</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20981102[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09515" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20981102">Yachida et al. (2010)</a> concluded that their data provided novel insights into the genetic features underlying pancreatic cancer progression and defined a broad time window of opportunity for early detection to prevent deaths from metastatic disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20981102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., Kang, Y., Fleming, J. B., Bardeesy, N., Asara, J. M., Haigis, M. C., DePinho, R. A., Cantley, L. C., Kimmelman, A. C. <strong>Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway.</strong> Nature 496: 101-105, 2013. Note: Erratum: Nature 499: 504 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23535601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23535601</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23535601[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12040" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23535601">Son et al. (2013)</a> reported the identification of a noncanonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumor growth. Whereas most cells use glutamate dehydrogenase (GLUD1; <a href="/entry/138130">138130</a>) to convert glutamine-derived glutamate into alpha-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1; <a href="/entry/138180">138180</a>). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP+ ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, <a href="#40" class="mim-tip-reference" title="Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., Kang, Y., Fleming, J. B., Bardeesy, N., Asara, J. M., Haigis, M. C., DePinho, R. A., Cantley, L. C., Kimmelman, A. C. <strong>Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway.</strong> Nature 496: 101-105, 2013. Note: Erratum: Nature 499: 504 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23535601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23535601</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23535601[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12040" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23535601">Son et al. (2013)</a> established that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23535601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a humanized genetically modified mouse model of PDAC, <a href="#37" class="mim-tip-reference" title="Rosenfeldt, M. T., O'Prey, J., Morton, J. P., Nixon, C., MacKay, G., Mrowinska, A., Au, A., Rai, T. S., Zheng, L., Ridgway, R., Adams, P. D., Anderson, K. I., Gottlieb, E., Sansom, O. J., Ryan, K. M. <strong>p53 status determines the role of autophagy in pancreatic tumour development.</strong> Nature 504: 296-300, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24305049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24305049</a>] [<a href="https://doi.org/10.1038/nature12865" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24305049">Rosenfeldt et al. (2013)</a> showed that autophagy's role in tumor development is intrinsically connected to the status of the tumor suppressor p53 (<a href="/entry/191170">191170</a>). Mice with pancreases containing an activated oncogenic allele of Kras, the most common mutational event in PDAC, developed a small number of precancerous lesions that stochastically developed into PDAC over time. However, mice also lacking the essential autophagy genes Atg5 (<a href="/entry/604261">604261</a>) or Atg7 (<a href="/entry/608760">608760</a>) accumulated low-grade, premalignant pancreatic intraepithelial neoplasia lesions, but progression to high-grade pancreatic intraepithelial neoplasias and PDAC was blocked. In marked contrast, in mice containing oncogenic Kras and lacking p53, loss of autophagy no longer blocked tumor progression but actually accelerated tumor onset, with metabolic analysis revealing enhanced glucose uptake and enrichment of anabolic pathways, which can fuel tumor growth. <a href="#37" class="mim-tip-reference" title="Rosenfeldt, M. T., O'Prey, J., Morton, J. P., Nixon, C., MacKay, G., Mrowinska, A., Au, A., Rai, T. S., Zheng, L., Ridgway, R., Adams, P. D., Anderson, K. I., Gottlieb, E., Sansom, O. J., Ryan, K. M. <strong>p53 status determines the role of autophagy in pancreatic tumour development.</strong> Nature 504: 296-300, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24305049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24305049</a>] [<a href="https://doi.org/10.1038/nature12865" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24305049">Rosenfeldt et al. (2013)</a> also show that treatment of mice with the autophagy inhibitor hydroxychloroquine significantly accelerates tumor formation in mice containing oncogenic Kras but lacking p53. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24305049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The pathogenesis of pancreatic ductal adenocarcinoma (PDA) requires high levels of autophagy, a conserved self-degradative process. <a href="#34" class="mim-tip-reference" title="Perera, R. M., Stoykova, S., Nicolay, B. N., Ross, K. N., Fitamant, J., Boukhali, M., Lengrand, J., Deshpande, V., Selig, M. K., Ferrone, C. R., Settleman, J., Stephanopoulos, G., Dyson, N. J., Zoncu, R., Ramaswamy, S., Haas, W., Bardeesy, N. <strong>Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism.</strong> Nature 524: 361-365, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168401[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature14587" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26168401">Perera et al. (2015)</a> showed that autophagy induction in PDA occurs as part of a broader transcriptional program that coordinates activation of lysosome biogenesis and function, and nutrient scavenging, mediated by the MiT/TFE family of transcription factors. In human PDA cells, the MiT/TFE proteins (MITF, <a href="/entry/156845">156845</a>; TFE3, <a href="/entry/314310">314310</a>; and TFEB, <a href="/entry/600744">600744</a>) are decoupled from regulatory mechanisms that control their cytoplasmic retention. Increased nuclear import in turn drives the expression of a coherent network of genes that induce high levels of lysosomal catabolic function essential for PDA growth. Unbiased global metabolite profiling revealed that MiT/TFE-dependent autophagy-lysosome activation is specifically required to maintain intracellular amino acid pools. <a href="#34" class="mim-tip-reference" title="Perera, R. M., Stoykova, S., Nicolay, B. N., Ross, K. N., Fitamant, J., Boukhali, M., Lengrand, J., Deshpande, V., Selig, M. K., Ferrone, C. R., Settleman, J., Stephanopoulos, G., Dyson, N. J., Zoncu, R., Ramaswamy, S., Haas, W., Bardeesy, N. <strong>Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism.</strong> Nature 524: 361-365, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168401[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature14587" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26168401">Perera et al. (2015)</a> concluded that their results identified the MiT/TFE proteins as master regulators of metabolic reprogramming in pancreatic cancer and demonstrated that transcriptional activation of clearance pathways converging on the lysosome is a novel hallmark of aggressive malignancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26168401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Seifert, L., Werba, G., Tiwari, S., Giao Ly, N. N., Alothman, S., Alqunaibit, D., Avanzi, A., Barilla, R., Daley, D., Greco, S. H., Torres-Hernandez, A., Pergamo, M., and 10 others. <strong>The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.</strong> Nature 532: 245-249, 2016. Note: Erratum: Nature 591: E28, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27049944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27049944</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27049944[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature17403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27049944">Seifert et al. (2016)</a> reported that the principal components of the necrosome, receptor-interacting proteins RIP1 (<a href="/entry/603453">603453</a>) and RIP3 (<a href="/entry/605817">605817</a>), are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Cytoplasmic SF3B3 (<a href="/entry/605592">605592</a>), a subunit of the histone deacetylase complex, was expressed in PDA in a RIP1/RIP3-dependent manner, and MINCLE (<a href="/entry/609962">609962</a>), its cognate receptor, was upregulated in tumor-infiltrating myeloid cells. Ligation of MINCLE by SAP130 promoted oncogenesis, whereas deletion of MINCLE protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumor microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or MINCLE is deleted. Accordingly, T cells, which are not protective against PDA progression in mice with intact RIP3 or MINCLE signaling, were reprogrammed into indispensable mediators of antitumor immunity in the absence of RIP3 or MINCLE. <a href="#38" class="mim-tip-reference" title="Seifert, L., Werba, G., Tiwari, S., Giao Ly, N. N., Alothman, S., Alqunaibit, D., Avanzi, A., Barilla, R., Daley, D., Greco, S. H., Torres-Hernandez, A., Pergamo, M., and 10 others. <strong>The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.</strong> Nature 532: 245-249, 2016. Note: Erratum: Nature 591: E28, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27049944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27049944</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27049944[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature17403" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27049944">Seifert et al. (2016)</a> concluded that their work described parallel networks of necroptosis-induced CXCL1 and MINCLE signaling that promote macrophage-induced adaptive immune suppression and thereby enable PDA progression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27049944" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., Nourse, C., Murtaugh, L. C., and 91 others. <strong>Genomic analyses identify molecular subtypes of pancreatic cancer.</strong> Nature 531: 47-52, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26909576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26909576</a>] [<a href="https://doi.org/10.1038/nature16965" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26909576">Bailey et al. (2016)</a> performed integrated genomic analysis of 456 pancreatic ductal adenocarcinomas and identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-beta, WNT, NOTCH, ROBO/SLIT signaling (see <a href="/entry/602430">602430</a>), G1/S transition, SWI-SNF (see <a href="/entry/603111">603111</a>), chromatin modification, DNA repair, and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathologic characteristics. Squamous tumors are enriched for TP53 (<a href="/entry/191170">191170</a>) and KDM6A (<a href="/entry/300128">300128</a>) mutations, upregulation of the TP63-delta-N (<a href="/entry/603273">603273</a>) transcriptional network, and hypermethylation of pancreatic endodermal cell fate-determining genes, and have a poor prognosis. Pancreatic progenitor tumors preferentially express genes involved in early pancreatic development (FOXA2 (<a href="/entry/600288">600288</a>)/FOXA3 (<a href="/entry/602295">602295</a>); PDX1, <a href="/entry/600733">600733</a>; and MNX1, <a href="/entry/142994">142994</a>). ADEX tumors displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2, <a href="/entry/604453">604453</a> and RBPJL, <a href="/entry/616104">616104</a>), and endocrine differentiation (NEUROD1, <a href="/entry/601724">601724</a> and NKX2-2, <a href="/entry/604612">604612</a>). Immunogenic tumors contained upregulated immune networks including pathways involved in acquired immune suppression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26909576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To study the role of glycan changes in pancreatic disease, <a href="#16" class="mim-tip-reference" title="Engle, D. D., Tiriac, H., Rivera, K. D., Pommier, A., Whalen, S., Oni, T. E., Alagesan, B., Lee, E. J., Yao, M. A., Lucito, M. S., Spielman, B., Da Silva, B., and 16 others. <strong>The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice.</strong> Science 364: 1156-1162, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31221853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31221853</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31221853[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.aaw3145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31221853">Engle et al. (2019)</a> inducibly expressed human fucosyltransferase-3 (FUT3; <a href="/entry/111100">111100</a>) and beta-1,3-galactosyltransferase-5 (B3GALT5; <a href="/entry/604066">604066</a>) in mice, reconstituting the glycan sialyl-Lewis, also known as carbohydrate antigen 19-9 (CA19-9). Notably, CA19-9 expression in mice resulted in rapid and severe pancreatitis with hyperactivation of epidermal growth factor receptor (EGFR) signaling. Mechanistically, CA19-9 modification of the matricellular protein fibulin-3 (FBLN3; <a href="/entry/601548">601548</a>) increased its interaction with EGFR, and blockade of fibulin-3, EGFR ligands, or CA19-9 prevented EGFR hyperactivation in organoids. CA19-9-mediated pancreatitis was reversible and could be suppressed with CA19-9 antibodies. CA19-9 also cooperated with the Kras(G12D) oncogene (<a href="/entry/190070#0003">190070.0003</a>) to produce aggressive pancreatic cancer. <a href="#16" class="mim-tip-reference" title="Engle, D. D., Tiriac, H., Rivera, K. D., Pommier, A., Whalen, S., Oni, T. E., Alagesan, B., Lee, E. J., Yao, M. A., Lucito, M. S., Spielman, B., Da Silva, B., and 16 others. <strong>The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice.</strong> Science 364: 1156-1162, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31221853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31221853</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31221853[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.aaw3145" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31221853">Engle et al. (2019)</a> concluded that their findings implicated CA19-9 in the etiology of pancreatitis and pancreatic cancer and nominated CA19-9 as a therapeutic target. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31221853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#47" class="mim-tip-reference" title="Yao, W., Rose, J. L., Wang, W., Seth, S., Jiang, H., Taguchi, A., Liu, J., Yan, L., Kapoor, A., Hou, P., Chen, Z., Wang, Q., and 26 others. <strong>Syndecan 1 is a critical mediator of macropinocytosis in pancreatic cancer.</strong> Nature 568: 410-414, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30918400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30918400</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30918400[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-019-1062-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30918400">Yao et al. (2019)</a> developed an unbiased functional target discovery platform to query oncogeneic KRAS-dependent changes of the pancreatic ductal adenocarcinoma surfaceome, which revealed syndecan-1 (SDC1; <a href="/entry/186355">186355</a>) as a protein that is upregulated at the cell surface by oncogenic KRAS. Localization of SDC1 at the cell surface, where it regulates macropinocytosis, an essential metabolic pathway that fuels pancreatic ductal adenocarcinoma cell growth, is essential for disease maintenance and progression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30918400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Notta, F., Chan-Seng-Yue, M., Lemire, M., Li, Y., Wilson, G. W., Connor, A. A., Denroche, R. E., Liang, S.-B., Brown, A. M. K., Kim, J. C., Wang, T., Simpson, J. T., and 34 others. <strong>A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns.</strong> Nature 538: 378-382, 2016. Note: Erratum: Nature 542: 124 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27732578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27732578</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27732578[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature19823" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27732578">Notta et al. (2016)</a> tracked changes in DNA copy number and their associated rearrangements in tumor-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumors analyzed harbored complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors was the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set off invasive cancer growth. <a href="#32" class="mim-tip-reference" title="Notta, F., Chan-Seng-Yue, M., Lemire, M., Li, Y., Wilson, G. W., Connor, A. A., Denroche, R. E., Liang, S.-B., Brown, A. M. K., Kim, J. C., Wang, T., Simpson, J. T., and 34 others. <strong>A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns.</strong> Nature 538: 378-382, 2016. Note: Erratum: Nature 542: 124 only, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27732578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27732578</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27732578[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature19823" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27732578">Notta et al. (2016)</a> concluded that these findings challenged the pancreatic intraepithelial neoplasm (PanIN) progression model of pancreatic cancer and provided insights into the mutational processes that give rise to these aggressive tumors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27732578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Aykut, B., Pushalkar, S., Chen, R., Li, Q., Abengozar, R., Kim, J. I., Shadaloey, S. A., Wu, D., Preiss, P., Verma, N., Guo, Y., Saxena, A., and 10 others. <strong>The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL.</strong> Nature 574: 264-267, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31578522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31578522</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31578522[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-019-1608-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31578522">Aykut et al. (2019)</a> showed that fungi migrate from the gut lumen to the pancreas and that this is implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA). PDA tumors in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue. The composition of the mycobiome of PDA tumors was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices. Specifically, the fungal community that infiltrated PDA tumors was markedly enriched for Malassezia species in both mice and humans. Ablation of the mycobiome was protective against tumor growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species, but not species in the genera Candida, Saccharomyces, or Aspergillus, accelerated oncogenesis. <a href="#4" class="mim-tip-reference" title="Aykut, B., Pushalkar, S., Chen, R., Li, Q., Abengozar, R., Kim, J. I., Shadaloey, S. A., Wu, D., Preiss, P., Verma, N., Guo, Y., Saxena, A., and 10 others. <strong>The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL.</strong> Nature 574: 264-267, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31578522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31578522</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31578522[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-019-1608-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31578522">Aykut et al. (2019)</a> also discovered that ligation of mannose-binding lectin (MBL2; <a href="/entry/154545">154545</a>), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 (<a href="/entry/120700">120700</a>) in the extratumoral compartment, or knockdown of C3AR (<a href="/entry/605246">605246</a>) in tumor cells, were both protective against tumor growth. In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl-null or C3-deficient mice. <a href="#4" class="mim-tip-reference" title="Aykut, B., Pushalkar, S., Chen, R., Li, Q., Abengozar, R., Kim, J. I., Shadaloey, S. A., Wu, D., Preiss, P., Verma, N., Guo, Y., Saxena, A., and 10 others. <strong>The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL.</strong> Nature 574: 264-267, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31578522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31578522</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31578522[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-019-1608-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31578522">Aykut et al. (2019)</a> concluded that their work showed that pathogenic fungi promote PDA by driving the complement cascade through the activation of MBL. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31578522" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Ferroptosis is a form of cell death that results from the catastrophic accumulation of lipid ROS. Oncogenic signaling elevates lipid ROS production in many tumor types and is counteracted by metabolites that are derived from the amino acid cysteine. <a href="#5" class="mim-tip-reference" title="Badgley, M. A., Kremer, D. M., Maurer, H. C., DelGiorno, K. E., Lee, H.-J., Purohit, V., Sagalovskiy, I. R., Ma, A., Kapilian, J., Firl, C. E. M., Decker, A. R., Sastra, S. A., and 18 others. <strong>Cysteine depletion induces pancreatic tumor ferroptosis in mice.</strong> Science 368: 85-89, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32241947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32241947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32241947[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.aaw9872" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32241947">Badgley et al. (2020)</a> showed that the import of oxidized cysteine (cystine) via system x(C)- is a critical dependency of PDAC. PDAC cells used cysteine to synthesize glutathione and coenzyme A, which, together, downregulate ferroptosis. Studying genetically engineered mice, <a href="#5" class="mim-tip-reference" title="Badgley, M. A., Kremer, D. M., Maurer, H. C., DelGiorno, K. E., Lee, H.-J., Purohit, V., Sagalovskiy, I. R., Ma, A., Kapilian, J., Firl, C. E. M., Decker, A. R., Sastra, S. A., and 18 others. <strong>Cysteine depletion induces pancreatic tumor ferroptosis in mice.</strong> Science 368: 85-89, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32241947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32241947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32241947[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.aaw9872" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32241947">Badgley et al. (2020)</a> found that the deletion of a system x(C)- subunit, Slc7a11 (<a href="/entry/607933">607933</a>), induced tumor-selective ferroptosis and inhibited PDAC growth. This was replicated through the administration of cyst(e)inase, a drug that depletes cysteine and cystine, demonstrating a translatable means to induce ferroptosis in PDAC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32241947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#46" class="mim-tip-reference" title="Yamamoto, K., Venida, A., Yano, J., Biancur, D. E., Kakiuchi, M., Gupta, S., Sohn, A. S. W., Mukhopadhyay, S., Lin, E. Y., Parker, S. J., Banh, R. S., Paulo, J. A., Wen, K. W., Debnath, J., Kim, G. E., Mancias, J. D., Fearon, D. T., Perera, R. M., Kimmelman, A. C. <strong>Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I.</strong> Nature 581: 100-105, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32376951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32376951</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32376951[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-020-2229-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32376951">Yamamoto et al. (2020)</a> showed that in PDAC, major histocompatibility complex class I (MHC-I; see <a href="/entry/142800">142800</a>) molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves the receptor NBR1 (<a href="/entry/166945">166945</a>). PDAC cells displayed reduced expression of MHC-I at the cell surface and instead demonstrated localization in autophagosomes and lysosomes. Inhibition of autophagy restored surface levels of MHC-I and led to improved antigen presentation, enhanced antitumor T cell responses, and reduced tumor growth in syngeneic host mice. The antitumor effects of autophagy inhibition were reversed by depleting CD8+ T cells or reducing surface expression of MHC-I. Inhibition of autophagy synergized with dual immune check-point blockade therapy and led to enhanced antitumor immune response. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32376951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Pancreatic Neuroendocrine Tumors</em></strong></p><p>
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<a href="#20" class="mim-tip-reference" title="Heaphy, C. M., de Wilde, R. F., Jiao, Y., Klein, A. P., Edil, B. H., Shi, C., Bettegowda, C., Rodriguez, F. J., Eberhart, C. G., Hebbar, S., Offerhaus, G. J., McLendon, R., and 13 others. <strong>Altered telomeres in tumors with ATRX and DAXX mutations.</strong> Science 333: 425 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21719641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21719641</a>] [<a href="https://doi.org/10.1126/science.1207313" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21719641">Heaphy et al. (2011)</a> evaluated telomere status in pancreatic neuroendocrine tumors (PanNETs) in which ATRX (<a href="/entry/300032">300032</a>) and DAXX (<a href="/entry/603186">603186</a>) mutational status had been determined through Sanger sequencing. Telomere-specific FISH revealed that 25 of 41 (61%) PanNETs displayed large, ultrabright telomere FISH signals, a nearly universal feature of the telomerase-independent telomere maintenance mechanism termed alternative lengthening of telomeres. ATRX and DAXX gene mutations both were significantly correlated with ALT positivity (P less than 0.008 for each gene). All 19 (100%) PanNETs with ATRX or DAXX gene mutations were ALT-positive, whereas 6 of 20 cases without detectable mutations were ALT-positive. To ascertain whether ATRX and DAXX gene mutations might be more generally associated with the ALT phenotype, <a href="#20" class="mim-tip-reference" title="Heaphy, C. M., de Wilde, R. F., Jiao, Y., Klein, A. P., Edil, B. H., Shi, C., Bettegowda, C., Rodriguez, F. J., Eberhart, C. G., Hebbar, S., Offerhaus, G. J., McLendon, R., and 13 others. <strong>Altered telomeres in tumors with ATRX and DAXX mutations.</strong> Science 333: 425 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21719641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21719641</a>] [<a href="https://doi.org/10.1126/science.1207313" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21719641">Heaphy et al. (2011)</a> examined 439 tumors of other types and found a strong correlation between inactivation of ATRX or DAXX and the ALT phenotype in unrelated tumor types. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21719641" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using mass spectrometry analyses, <a href="#31" class="mim-tip-reference" title="Melo, S. A., Luecke, L. B., Kahlert, C., Fernandez, A. F., Gammon, S. T., Kaye, J., LeBleu, V. S., Mittendorf, E. A., Weitz, J., Rahbari, N., Reissfelder, C., Pilarsky, C., Fraga, M. F., Piwnica-Worms, D., Kalluri, R. <strong>Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.</strong> Nature 523: 177-182, 2015. Note: Erratum: Nature 610: E15-E17, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26106858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26106858</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26106858[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature14581" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26106858">Melo et al. (2015)</a> identified a cell surface proteoglycan, glypican-1 (GPC1; <a href="/entry/600395">600395</a>), specifically enriched on cancer cell-derived exosomes. GPC1-positive circulating exosomes were monitored and isolated using flow cytometry from the serum of patients and mice with cancer. GPC1-positive circulating exosomes were detected in the serum of patients with pancreatic cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreatic disease from patients with early- and late-stage pancreatic cancer. Levels of GPC1-positive circulating exosomes correlated with tumor burden and the survival of pre- and post-surgical patients. GPC1-positive circulating exosomes from patients and from mice with spontaneous pancreatic tumors carry specific KRAS (<a href="/entry/190070">190070</a>) mutations, and reliably detected pancreatic intraepithelial lesions in mice despite negative signals by MRI. <a href="#31" class="mim-tip-reference" title="Melo, S. A., Luecke, L. B., Kahlert, C., Fernandez, A. F., Gammon, S. T., Kaye, J., LeBleu, V. S., Mittendorf, E. A., Weitz, J., Rahbari, N., Reissfelder, C., Pilarsky, C., Fraga, M. F., Piwnica-Worms, D., Kalluri, R. <strong>Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.</strong> Nature 523: 177-182, 2015. Note: Erratum: Nature 610: E15-E17, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26106858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26106858</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26106858[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature14581" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26106858">Melo et al. (2015)</a> concluded that GPC1-positive circulating exosomes may serve as a potential noninvasive diagnostic and screening tool to detect early stages of pancreatic cancer to facilitate possible curative surgical therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26106858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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<a href="#3" class="mim-tip-reference" title="Amundadottir, L., Kraft, P., Stolzenberg-Solomon, R. Z., Fuchs, C. S., Petersen, G. M., Arslan, A. A., Bueno-de-Mesquita, H. B., Gross, M., Helzlsouer, K., Jacobs, E. J., LaCroix, A., Zheng, W., and 59 others. <strong>Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.</strong> Nature Genet. 41: 986-990, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19648918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19648918</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19648918[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19648918">Amundadottir et al. (2009)</a> conducted a 2-stage genomewide association study of pancreatic cancer, genotyping over 500,000 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus 1 hospital-based case-control study. The authors conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from 8 case-control studies, adjusting for study, sex, ancestry, and 5 principal components. They identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs505922;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs505922</a> (combined P = 5.37 x 10(8); multiplicative per-allele odds ratio 1.20; 95% CI 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene (<a href="/entry/110300">110300</a>). The protective allele T for <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs505922;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs505922</a> is in complete linkage disequilibrium with the O allele of the ABO locus, consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19648918" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#35" class="mim-tip-reference" title="Petersen, G. M., Amundadottir, L., Fuchs, C. S., Kraft, P., Stolzenberg-Solomon, R. Z., Jacobs, K. B., Arslan, A. A., Bueno-de-Mesquita, H. B., Gallinger, S., Gross, M., Helzlsouer, K., Holly, E. A., and 61 others. <strong>A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.</strong> Nature Genet. 42: 224-228, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20101243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20101243</a>] [<a href="https://doi.org/10.1038/ng.522" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20101243">Petersen et al. (2010)</a> conducted a genomewide association study of pancreatic cancer in 3,851 affected individuals and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry, and 5 principal components, <a href="#35" class="mim-tip-reference" title="Petersen, G. M., Amundadottir, L., Fuchs, C. S., Kraft, P., Stolzenberg-Solomon, R. Z., Jacobs, K. B., Arslan, A. A., Bueno-de-Mesquita, H. B., Gallinger, S., Gross, M., Helzlsouer, K., Holly, E. A., and 61 others. <strong>A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.</strong> Nature Genet. 42: 224-228, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20101243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20101243</a>] [<a href="https://doi.org/10.1038/ng.522" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20101243">Petersen et al. (2010)</a> identified 8 SNPs that map to 3 loci on chromosomes 13q22.1, 1q32.1, and 5p15.33. Two correlated SNPs, <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs9543325;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs9543325</a> (p = 3.27 x 10(-11), per-allele odds ratio 1.26, 95% CI 1.18-1.35) and <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs9564966;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs9564966</a> (p = 5.86 x 10(-8), per-allele odds ratio 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2 (<a href="/entry/604453">604453</a>), and the strongest signal was at <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs3790844;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs3790844</a> (p = 2.45 x 10(-10), per-allele odds ratio 0.77, 95% CI 0.71-0.84). A single SNP, <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs401681;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs401681</a> (p = 3.66 x 10(-7), per-allele odds ratio 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L (<a href="/entry/612585">612585</a>)-TERT (<a href="/entry/187270">187270</a>) locus on 5p15.33, which is associated with multiple cancers. <a href="#35" class="mim-tip-reference" title="Petersen, G. M., Amundadottir, L., Fuchs, C. S., Kraft, P., Stolzenberg-Solomon, R. Z., Jacobs, K. B., Arslan, A. A., Bueno-de-Mesquita, H. B., Gallinger, S., Gross, M., Helzlsouer, K., Holly, E. A., and 61 others. <strong>A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.</strong> Nature Genet. 42: 224-228, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20101243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20101243</a>] [<a href="https://doi.org/10.1038/ng.522" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20101243">Petersen et al. (2010)</a> concluded that their study identified common susceptibility loci for pancreatic cancer that warrant follow-up studies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20101243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By genomewide association analysis, <a href="#49" class="mim-tip-reference" title="Zheng, J., Huang, X., Tan, W., Yu, D., Du, Z., Chang, J., Wei, L., Han, Y., Wang, C., Che, X., Zhou, Y., Miao, X., and 12 others. <strong>Pancreatic cancer risk variant in LINC00673 creates a miR-1231 binding site and interferes with PTPN11 degradation.</strong> Nature Genet. 48: 747-757, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27213290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27213290</a>] [<a href="https://doi.org/10.1038/ng.3568" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27213290">Zheng et al. (2016)</a> identified a G-A SNP in exon 4 of the LINC00673 gene (<a href="/entry/617079">617079</a>) (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11655237;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs11655237</a>) that was associated with susceptibility to pancreatic ductal adenocarcinoma in a Han Chinese population. The A allele of <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11655237;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs11655237</a> was predicted to change the local structure of LINC00673 and to introduce a potential binding site for microRNA-1231 (MIR1231; <a href="/entry/617040">617040</a>). Reporter gene assays confirmed that MIR1231 inhibited expression of LINC00673 with the A allele of <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11655237;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs11655237</a> in a dose-dependent manner, but it had no effect on LINC00673 with the G allele of <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11655237;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs11655237</a>. Allele-specific targeting of LINC00673 by MIR1231 inhibited LINC00673 regulation of the PTPN11 (<a href="/entry/176876">176876</a>) pathway, thereby promoting tumor cell growth in individuals carrying the A allele of <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11655237;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs11655237</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27213290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Mutation in KRAS2</em></strong></p><p>
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Point mutations in codon 12 of the KRAS2 gene (<a href="/entry/190070">190070</a>) occur in 75 to 90% of pancreatic cancers (<a href="#2" class="mim-tip-reference" title="Almoguera, C., Shibata, D., Forrester, K., Martin, J., Arnheim, N., Perucho, M. <strong>Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes.</strong> Cell 53: 549-554, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2453289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2453289</a>] [<a href="https://doi.org/10.1016/0092-8674(88)90571-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2453289">Almoguera et al., 1988</a>), and also occur in foci of pancreatic intraepithelial neoplasia, a putative precursor lesion of pancreatic cancer (<a href="#21" class="mim-tip-reference" title="Hruban, R. H., Goggins, M., Parsons, J., Kern, S. E. <strong>Progression model for pancreatic cancer.</strong> Clin. Cancer Res. 6: 2969-2972, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10955772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10955772</a>]" pmid="10955772">Hruban et al., 2000</a>). <a href="#17" class="mim-tip-reference" title="Evans, J. P., Burke, W., Chen, R., Bennett, R. L., Schmidt, R. A., Patchen Dellinger, E., Kimmey, M., Crispin, D., Brentnall, T. A., Byrd, D. R. <strong>Familial pancreatic adenocarcinoma: association with diabetes and early molecular diagnosis.</strong> J. Med. Genet. 32: 330-335, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7616537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7616537</a>] [<a href="https://doi.org/10.1136/jmg.32.5.330" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7616537">Evans et al. (1995)</a> analyzed this gene in pancreatic tumors from patients in a large pedigree with autosomal dominant pancreatic cancer preceded by diabetes and exocrine insufficiency. The presence of diabetes, often years before the diagnosis of cancer, allowed identification of those who had inherited the predisposing allele. Pancreatic tissue from all 3 persons analyzed showed KRAS point mutations, and in all 3 the mutations were located in codon 13. The observation of several different KRAS mutations in pancreatic tumors from this family and the presence of only wildtype KRAS in normal tissue clearly showed that the mutant KRAS gene was not the germline event underlying pancreatic cancer in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10955772+2453289+7616537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Mutation in CDKN2A</em></strong></p><p>
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Although KRAS mutations are found in 85% or more of cases of pancreatic adenocarcinoma, and p53 mutations (<a href="/entry/191170">191170</a>) in at least of 50% of cases, little is known of the genetic changes that occur in pancreatic carcinogenesis. <a href="#12" class="mim-tip-reference" title="Caldas, C., Hahn, S. A., da Costa, L. T., Redston, M. S., Schutte, M., Seymour, A. B., Weinstein, C. L., Hruban, R. H., Yeo, C. J., Kern, S. E. <strong>Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma.</strong> Nature Genet. 8: 27-32, 1994. Note: Erratum: Nature Genet. 8: 410 only, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726912</a>] [<a href="https://doi.org/10.1038/ng0994-27" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7726912">Caldas et al. (1994)</a> described experiments suggesting that mutation in the p16 gene (CDKN2A; <a href="/entry/600160">600160</a>), which they referred to as MTS1, is a frequent cause of pancreatic adenocarcinoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7726912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Liu, Q., Yan, Y.-X., McClure, M., Nakagawa, H., Fujimura, F., Rustgi, A. K. <strong>MTS-1 (CDKN2) tumor suppressor gene deletions are a frequent event in esophagus squamous cancer and pancreatic adenocarcinoma cell lines.</strong> Oncogene 10: 619-622, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7845688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7845688</a>]" pmid="7845688">Liu et al. (1995)</a> found that 50% of pancreatic cancer cell lines had deletions of both exons 1 and 2 of the CDKN2 gene; furthermore, an additional 30% of pancreatic cancer cell lines harbored point mutations or microdeletions based on DNA sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7845688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Further evidence of the role of CDKN2 in pancreatic tumorigenesis was provided by <a href="#44" class="mim-tip-reference" title="Whelan, A. J., Bartsch, D., Goodfellow, P. J. <strong>Brief report: a familial syndrome of pancreatic cancer and melanoma with a mutation in the CDKN2 tumor-suppressor gene.</strong> New Eng. J. Med. 333: 975-977, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7666917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7666917</a>] [<a href="https://doi.org/10.1056/NEJM199510123331505" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7666917">Whelan et al. (1995)</a>, who described a kindred with an increased risk of pancreatic cancers, melanomas, and possibly additional types of tumors cosegregating with a CDKN2 mutation (<a href="/entry/600160#0005">600160.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7666917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a population-based study, <a href="#19" class="mim-tip-reference" title="Ghiorzo, P., Fornarini, G., Sciallero, S., Battistuzzi, L., Belli, F., Bernard, L., Bonelli, L., Borgonovo, G., Bruno, W., De Cian, F., DeCensi, A., Filauro, M., and 11 others. <strong>CDKN2A is the main susceptibility gene in Italian pancreatic cancer families.</strong> J. Med. Genet. 49: 164-170, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22368299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22368299</a>] [<a href="https://doi.org/10.1136/jmedgenet-2011-100281" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22368299">Ghiorzo et al. (2012)</a> identified CDKN2A mutations in 13 (5.7%) of 225 Italian patients with pancreatic cancer. Six patients carried the common G101W mutation (<a href="/entry/600160#0005">600160.0005</a>), which was the most common mutation. Among the 16 probands with a family history of cancer, including pancreatic cancer and melanoma, 5 (31%) were found to carry CDKN2A mutations. The mutation frequency ranged from 20% in families with 2 affected members to 50% in families with 3 affected members. The findings suggested that CDKN2A is the main susceptibility gene in Italian families with pancreatic cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22368299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Mutation in BRCA2</em></strong></p><p>
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See <a href="/entry/613347">613347</a> for information on pancreatic cancer susceptibility due to mutation in the BRCA2 gene (<a href="/entry/600185">600185</a>).</p><p><strong><em>Mutation in PALLD</em></strong></p><p>
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See <a href="/entry/606856">606856</a> for information on autosomal dominant pancreatic cancer due to mutation in the PALLD gene (<a href="/entry/608092">608092</a>).</p><p><strong><em>Mutation in PALB2</em></strong></p><p>
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See <a href="/entry/606856">606856</a> for information on pancreatic cancer susceptibility due to mutation in the PALB2 gene (<a href="/entry/610355">610355</a>).</p><p><strong><em>Mutation in BRCA1</em></strong></p><p>
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<a href="#1" class="mim-tip-reference" title="Al-Sukhni, W., Rothenmund, H., Eppel Borgida, A., Zogopoulos, G., O'Shea, A.-M., Pollett, A., Gallinger, S. <strong>Germline BRCA1 mutations predispose to pancreatic adenocarcinoma.</strong> Hum. Genet. 124: 271-278, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18762988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18762988</a>] [<a href="https://doi.org/10.1007/s00439-008-0554-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18762988">Al-Sukhni et al. (2008)</a> found loss of heterozygosity at the BRCA1 locus (<a href="/entry/113705">113705</a>) in pancreatic tumor DNA from 5 (71%) of 7 patients with pancreatic cancer who carried a heterozygous germline BRCA1 mutation (see, e.g., <a href="/entry/113705#0003">113705.0003</a> and <a href="/entry/113705#0018">113705.0018</a>). Pancreatic tumor DNA was available for sequencing in 4 cases, and 3 demonstrated loss of the wildtype allele. In contrast, only 1 (11%) of 9 patients with sporadic pancreatic cancer and no germline BRCA1 mutations showed LOH at the BRCA1 locus. <a href="#1" class="mim-tip-reference" title="Al-Sukhni, W., Rothenmund, H., Eppel Borgida, A., Zogopoulos, G., O'Shea, A.-M., Pollett, A., Gallinger, S. <strong>Germline BRCA1 mutations predispose to pancreatic adenocarcinoma.</strong> Hum. Genet. 124: 271-278, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18762988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18762988</a>] [<a href="https://doi.org/10.1007/s00439-008-0554-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18762988">Al-Sukhni et al. (2008)</a> concluded that BRCA1 germline mutations likely predispose to the development of pancreatic cancer, and suggested that individuals with these mutations be considered for pancreatic cancer-screening programs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18762988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Mutation in Axon Guidance Pathway Genes</em></strong></p><p>
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<a href="#10" class="mim-tip-reference" title="Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., Wu, J., Chang, D. K., Cowley, M. J., and 116 others. <strong>Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.</strong> Nature 491: 399-405, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23103869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23103869</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23103869[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature11547" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23103869">Biankin et al. (2012)</a> performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort of 142 patients with early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumors identified substantial heterogeneity with 2,016 nonsilent mutations and 1,628 copy number variations. <a href="#10" class="mim-tip-reference" title="Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., Wu, J., Chang, D. K., Cowley, M. J., and 116 others. <strong>Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.</strong> Nature 491: 399-405, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23103869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23103869</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23103869[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature11547" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23103869">Biankin et al. (2012)</a> defined 16 significantly mutated genes, reaffirming known mutations (KRAS, <a href="/entry/190070">190070</a>; TP53, <a href="/entry/191170">191170</a>; CDKN2A, <a href="/entry/600160">600160</a>; SMAD4, <a href="/entry/600993">600993</a>; MLL3, <a href="/entry/606833">606833</a>; TGFBR2, <a href="/entry/190182">190182</a>; ARID1A, <a href="/entry/603024">603024</a>; and SF3B1, <a href="/entry/605590">605590</a>), and uncovered novel mutated genes including additional genes involved in chromatin modification (EPC1, <a href="/entry/610999">610999</a> and ARID2, <a href="/entry/609539">609539</a>), DNA damage repair (ATM; <a href="/entry/607585">607585</a>), and other mechanisms (ZIM2 (see <a href="/entry/601483">601483</a>); MAP2K4, <a href="/entry/601335">601335</a>; NALCN, <a href="/entry/611549">611549</a>; SLC16A4, <a href="/entry/603878">603878</a>; and MAGEA6, <a href="/entry/300176">300176</a>). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signaling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. <a href="#10" class="mim-tip-reference" title="Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., Wu, J., Chang, D. K., Cowley, M. J., and 116 others. <strong>Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.</strong> Nature 491: 399-405, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23103869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23103869</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23103869[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature11547" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23103869">Biankin et al. (2012)</a> also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO (see <a href="/entry/603742">603742</a>) signaling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23103869" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Mutation in UPF1</em></strong></p><p>
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<a href="#25" class="mim-tip-reference" title="Liu, C., Karam, R., Zhou, Y., Su, F., Ji, Y., Li, G., Xu, G., Lu, L., Wang, C., Song, M., Zhu, J., Wang, Y., Zhao, Y., Foo, W. C., Zuo, M., Valasek, M. A., Javle, M., Wilkinson, M. F., Lu, Y. <strong>The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma.</strong> Nature Med. 20: 596-598, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24859531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24859531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24859531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.3548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24859531">Liu et al. (2014)</a> identified mutations in the UPF1 gene (<a href="/entry/601430">601430</a>) in pancreatic adenosquamous carcinoma (ASC) tumors from 18 of 23 patients. <a href="#25" class="mim-tip-reference" title="Liu, C., Karam, R., Zhou, Y., Su, F., Ji, Y., Li, G., Xu, G., Lu, L., Wang, C., Song, M., Zhu, J., Wang, Y., Zhao, Y., Foo, W. C., Zuo, M., Valasek, M. A., Javle, M., Wilkinson, M. F., Lu, Y. <strong>The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma.</strong> Nature Med. 20: 596-598, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24859531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24859531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24859531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.3548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24859531">Liu et al. (2014)</a> also tested 3 other nonsense-mediated RNA decay (NMD) genes--UPF2 (<a href="/entry/605529">605529</a>), UPF3A (<a href="/entry/605530">605530</a>), and UPF3B (<a href="/entry/300298">300298</a>)--but did not detect mutations. The UPF1 mutations were somatic in origin, as they were not present in matched normal pancreatic tissues from the 18 patients. UPF1 mutations were also not detectable in 29 non-ASC pancreatic tumors and in 21 lung squamous cell carcinomas that were tested. <a href="#25" class="mim-tip-reference" title="Liu, C., Karam, R., Zhou, Y., Su, F., Ji, Y., Li, G., Xu, G., Lu, L., Wang, C., Song, M., Zhu, J., Wang, Y., Zhao, Y., Foo, W. C., Zuo, M., Valasek, M. A., Javle, M., Wilkinson, M. F., Lu, Y. <strong>The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma.</strong> Nature Med. 20: 596-598, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24859531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24859531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24859531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.3548" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24859531">Liu et al. (2014)</a> concluded that UPF1 mutations are a unique signature of most pancreatic adenosquamous carcinomas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24859531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Multigene Studies</em></strong></p><p>
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<a href="#48" class="mim-tip-reference" title="Zhen, D. B., Rabe, K. G., Gallinger, S., Syngal, S., Schwartz, A. G., Goggins, M. G., Hruban, R. H., Cote, M. L., McWilliams, R. R., Roberts, N. J., Cannon-Albright, L. A., Li, D., Moyes, K., Wenstrup, R. J., Hartman, A.-R., Seminara, D., Klein, A. P., Petersen, G. M. <strong>BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study.</strong> Genet. Med. 17: 569-577, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25356972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25356972</a>] [<a href="https://doi.org/10.1038/gim.2014.153" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25356972">Zhen et al. (2015)</a> tested germline DNA from 727 unrelated probands with pancreatic cancer and a positive family history for mutations in BRCA1 (<a href="/entry/113705">113705</a>) and BRCA2 (<a href="/entry/600185">600185</a>) (including deletions and rearrangements), PALB2 (<a href="/entry/610355">610355</a>), and CDKN2A (<a href="/entry/600160">600160</a>). Among these probands, 521 met criteria for familial pancreatic cancer (FPC; at least 2 affected first-degree relatives). The prevalence of deleterious mutations, excluding variants of unknown significance, among FPC probands was BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. FPC probands carried more mutations in the 4 genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%; OR = 2.40, 95% CI 1.06-5.44, p = 0.03). The probability of testing positive for deleterious mutations in any of the 4 genes ranged up to 10.4%, depending on family history of cancers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25356972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#43" class="mim-tip-reference" title="Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., Quek, K., Quinn, M. C. J., Robertson, A. J., and 78 others. <strong>Whole genomes redefine the mutational landscape of pancreatic cancer.</strong> Nature 518: 495-501, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25719666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25719666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25719666[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature14169" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25719666">Waddell et al. (2015)</a> performed whole-genome sequencing and copy number variation analysis of 100 pancreatic ductal adenocarcinomas. Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A, and ROBO2, <a href="/entry/602431">602431</a>) and new candidate drivers of pancreatic carcinogenesis (KDM6A, <a href="/entry/300128">300128</a> and PREX2, <a href="/entry/612139">612139</a>). Patterns of structural variation classified pancreatic ductal adenocarcinomas into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered, and unstable. A significant proportion harbored focal amplifications, many of which contained druggable oncogenes but at low individual patient prevalence. Genomic instability cosegregated with inactivation of DNA maintenance genes (BRCA1, BRCA2, or PALB2) and a mutational signature of DNA damage repair deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25719666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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Using data from genomewide association studies (GWAS) of 9,013 affected individuals and 12,452 control individuals of European ancestry, <a href="#22" class="mim-tip-reference" title="Jermusyk, A., Zhong, J., Connelly, K. E., Gordon, N., Perera, S., Abdolalizadeh, E., Zhang, T., O'Brien, A., Hoskins, J. W., Collins, I., Eiser, D., Yuan, C., and 15 others. <strong>A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and secretion and confers risk of pancreatic cancer.</strong> Am. J. Hum. Genet. 108: 1852-1865, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34559995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34559995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34559995[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2021.09.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34559995">Jermusyk et al. (2021)</a> fine-mapped a pancreatic cancer risk locus on chromosome 16q23.1 and identified a region containing the SNP <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs72802365;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs72802365</a> as a candidate locus. A 584-bp deletion variant in the region deleted exon 6 of CTRB2 (<a href="/entry/619620">619620</a>), resulting in a truncated 166-amino acid protein lacking the C chain of full-length CTRB2, including 1 of 3 amino acids in the catalytic triad, ser213. Functional characterization revealed that the truncated CTRB2 protein lost chymotrypsin activity, was not secreted, and accumulated intracellularly in the endoplasmic reticulum (ER). Differential expression analysis showed that ER stress pathways were upregulated in pancreatic tissue from carriers of the CTRB2 variant, leading to increased levels of ER stress and altered translational activity in pancreas. Fluorescence-tagged truncated CTRB2 protein was retained in the ER, resulting in increased expression of ER pathway-related genes in transfected pancreatic cells, leading to ER stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34559995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Pancreatic Neuroendocrine Tumors</em></strong></p><p>
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<a href="#23" class="mim-tip-reference" title="Jiao, Y., Shi, C., Edil, B. H., de Wilde, R. F., Klimstra, D. S., Maitra, A., Schulick, R. D., Tang, L. H., Wolfgang, C. L., Choti, M. A., Velculescu, V. E., Diaz, L. A., Jr., Vogelstein, B., Kinzler, K. W., Hruban, R. H., Papadopoulos, N. <strong>DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.</strong> Science 331: 1199-1203, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21252315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21252315</a>] [<a href="https://doi.org/10.1126/science.1200609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21252315">Jiao et al. (2011)</a> explored the genetic basis of pancreatic neuroendocrine tumors (PanNETs) by determining the exomic sequence of 10 nonfamilial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. The most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN1 (<a href="/entry/613733">613733</a>), and 43% had mutations in genes encoding either of the 2 subunits of a transcription/chromatin remodeling complex consisting of DAXX (death domain-associated protein, <a href="/entry/603186">603186</a>) and ATRX (<a href="/entry/300032">300032</a>). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis. <a href="#23" class="mim-tip-reference" title="Jiao, Y., Shi, C., Edil, B. H., de Wilde, R. F., Klimstra, D. S., Maitra, A., Schulick, R. D., Tang, L. H., Wolfgang, C. L., Choti, M. A., Velculescu, V. E., Diaz, L. A., Jr., Vogelstein, B., Kinzler, K. W., Hruban, R. H., Papadopoulos, N. <strong>DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.</strong> Science 331: 1199-1203, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21252315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21252315</a>] [<a href="https://doi.org/10.1126/science.1200609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21252315">Jiao et al. (2011)</a> also found mutations in genes in the mTOR (<a href="/entry/601231">601231</a>) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatments with mTOR inhibitors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21252315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>When Billy Carter, brother of President Jimmy Carter, died of pancreatic cancer in 1988, the news media reported that his sister Ruth Carter Stapleton, evangelist and faith healer, had died of pancreatic cancer at age 54 and their mother of pancreatic, bone, and breast cancer at age 85. In the New York Times of December 1, 1989, it was announced that President Carter's last surviving sib, Gloria Carter Spann, was found to be suffering from pancreatic cancer, 'the same disease that killed their father, sister and brother and contributed to the death of their mother.' The possibility of environmental causation might be raised, e.g., an agricultural insecticide or an oncogenic agent such as aflatoxin.</p>
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<p><a href="#33" class="mim-tip-reference" title="Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., Frese, K. K., DeNicola, G., and 25 others. <strong>Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer.</strong> Science 324: 1457-1461, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19460966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19460966</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19460966[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1171362" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19460966">Olive et al. (2009)</a> studied a mouse model of pancreatic ductal adenocarcinoma (PDA) that is refractory to the clinically used drug gemcitabine, and found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. <a href="#33" class="mim-tip-reference" title="Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., Frese, K. K., DeNicola, G., and 25 others. <strong>Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer.</strong> Science 324: 1457-1461, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19460966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19460966</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19460966[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1171362" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19460966">Olive et al. (2009)</a> tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibition of the Hedgehog cellular signaling pathway. The combination of therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. <a href="#33" class="mim-tip-reference" title="Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., Frese, K. K., DeNicola, G., and 25 others. <strong>Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer.</strong> Science 324: 1457-1461, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19460966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19460966</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19460966[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1171362" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19460966">Olive et al. (2009)</a> concluded that inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19460966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#MacDermott1973" class="mim-tip-reference" title="MacDermott, R. P., Kramer, P. <strong>Adenocarcinoma of the pancreas in 4 siblings.</strong> Gastroenterology 65: 137-139, 1973.">MacDermott and Kramer (1973)</a>
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<a id="1" class="mim-anchor"></a>
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|
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Al-Sukhni, W., Rothenmund, H., Eppel Borgida, A., Zogopoulos, G., O'Shea, A.-M., Pollett, A., Gallinger, S.
|
|
<strong>Germline BRCA1 mutations predispose to pancreatic adenocarcinoma.</strong>
|
|
Hum. Genet. 124: 271-278, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18762988/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18762988</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18762988" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-008-0554-0" target="_blank">Full Text</a>]
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Almoguera, C., Shibata, D., Forrester, K., Martin, J., Arnheim, N., Perucho, M.
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|
<strong>Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes.</strong>
|
|
Cell 53: 549-554, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2453289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2453289</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2453289" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0092-8674(88)90571-5" target="_blank">Full Text</a>]
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Amundadottir, L., Kraft, P., Stolzenberg-Solomon, R. Z., Fuchs, C. S., Petersen, G. M., Arslan, A. A., Bueno-de-Mesquita, H. B., Gross, M., Helzlsouer, K., Jacobs, E. J., LaCroix, A., Zheng, W., and 59 others.
|
|
<strong>Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.</strong>
|
|
Nature Genet. 41: 986-990, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19648918/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19648918</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19648918[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19648918" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.429" target="_blank">Full Text</a>]
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Aykut, B., Pushalkar, S., Chen, R., Li, Q., Abengozar, R., Kim, J. I., Shadaloey, S. A., Wu, D., Preiss, P., Verma, N., Guo, Y., Saxena, A., and 10 others.
|
|
<strong>The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL.</strong>
|
|
Nature 574: 264-267, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31578522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31578522</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31578522[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31578522" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s41586-019-1608-2" target="_blank">Full Text</a>]
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Badgley, M. A., Kremer, D. M., Maurer, H. C., DelGiorno, K. E., Lee, H.-J., Purohit, V., Sagalovskiy, I. R., Ma, A., Kapilian, J., Firl, C. E. M., Decker, A. R., Sastra, S. A., and 18 others.
|
|
<strong>Cysteine depletion induces pancreatic tumor ferroptosis in mice.</strong>
|
|
Science 368: 85-89, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32241947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32241947</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32241947[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32241947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.aaw9872" target="_blank">Full Text</a>]
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Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., Nourse, C., Murtaugh, L. C., and 91 others.
|
|
<strong>Genomic analyses identify molecular subtypes of pancreatic cancer.</strong>
|
|
Nature 531: 47-52, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26909576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26909576</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26909576" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature16965" target="_blank">Full Text</a>]
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Banke, M. G., Mulvihill, J. J., Aston, C. E.
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<strong>Inheritance of pancreatic cancer in pancreatic cancer-prone families.</strong>
|
|
Med. Clin. North Am. 84: 677-690, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10872424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10872424</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10872424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0025-7125(05)70250-9" target="_blank">Full Text</a>]
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Beatty, G. L., Chiorean, E. G., Fishman, M. P., Saboury, B., Teitelbaum, U. R., Sun, W., Huhn, R. D., Song, W., Li, D., Sharp, L. L., Torigian, D. A., O'Dwyer, P. J., Vonderheide, R. H.
|
|
<strong>CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans.</strong>
|
|
Science 331: 1612-1616, 2011.
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21436454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21436454</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21436454[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21436454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1198443" target="_blank">Full Text</a>]
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|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Berman2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Berman, D. M., Karhadkar, S. S., Maitra, A., Montes de Oca, R., Gerstenblith, M. R., Briggs, K., Parker, A. R., Shimada, Y., Eshleman, J. R., Watkins, D. N., Beachy, P. A.
|
|
<strong>Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours.</strong>
|
|
Nature 425: 846-851, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520411/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520411</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520411" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature01972" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Biankin2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., Wu, J., Chang, D. K., Cowley, M. J., and 116 others.
|
|
<strong>Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.</strong>
|
|
Nature 491: 399-405, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23103869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23103869</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23103869[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23103869" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature11547" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Boring1993" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Boring, C. C., Squires, T. S., Tong, T.
|
|
<strong>Cancer statistics, 1993.</strong>
|
|
CA Cancer J. Clin. 43: 7-26, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8422609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8422609</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8422609" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3322/canjclin.43.1.7" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Caldas1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Caldas, C., Hahn, S. A., da Costa, L. T., Redston, M. S., Schutte, M., Seymour, A. B., Weinstein, C. L., Hruban, R. H., Yeo, C. J., Kern, S. E.
|
|
<strong>Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma.</strong>
|
|
Nature Genet. 8: 27-32, 1994. Note: Erratum: Nature Genet. 8: 410 only, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7726912/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7726912</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7726912" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0994-27" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Campbell2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Campbell, P. J., Yachida, S., Mudie, L. J., Stephens, P. J., Pleasance, E. D., Stebbings, L. A., Morsberger, L. A., Latimer, C., McLaren, S., Lin, M.-L., McBride, D. J., Varela, I., and 13 others.
|
|
<strong>The patterns and dynamics of genomic instability in metastatic pancreatic cancer.</strong>
|
|
Nature 467: 1109-1113, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20981101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20981101</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20981101[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20981101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature09460" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Dey2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Dey, P., Baddour, J., Muller, F., Wu, C. C., Wang, H., Liao, W.-T., Lan, Z., Chen, A., Gutschner, T., Kang, Y., Fleming, J., Satani, N., and 13 others.
|
|
<strong>Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer.</strong>
|
|
Nature 542: 119-123, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28099419/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28099419</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28099419[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28099419" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature21052" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Ehrenthal1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ehrenthal, D., Haeger, L., Griffin, T., Compton, C.
|
|
<strong>Familial pancreatic adenocarcinoma in three generations: a case report and a review of the literature.</strong>
|
|
Cancer 59: 1661-1664, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3828965/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3828965</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3828965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1097-0142(19870501)59:9<1661::aid-cncr2820590923>3.0.co;2-h" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Engle2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Engle, D. D., Tiriac, H., Rivera, K. D., Pommier, A., Whalen, S., Oni, T. E., Alagesan, B., Lee, E. J., Yao, M. A., Lucito, M. S., Spielman, B., Da Silva, B., and 16 others.
|
|
<strong>The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice.</strong>
|
|
Science 364: 1156-1162, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31221853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31221853</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31221853[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31221853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.aaw3145" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Evans1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Evans, J. P., Burke, W., Chen, R., Bennett, R. L., Schmidt, R. A., Patchen Dellinger, E., Kimmey, M., Crispin, D., Brentnall, T. A., Byrd, D. R.
|
|
<strong>Familial pancreatic adenocarcinoma: association with diabetes and early molecular diagnosis.</strong>
|
|
J. Med. Genet. 32: 330-335, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7616537/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7616537</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7616537" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.32.5.330" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Friedman1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Friedman, J. M., Fialkow, P. J.
|
|
<strong>Familial carcinoma of the pancreas.</strong>
|
|
Clin. Genet. 9: 463-469, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1269168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1269168</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1269168" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1399-0004.1976.tb01598.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Ghiorzo2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ghiorzo, P., Fornarini, G., Sciallero, S., Battistuzzi, L., Belli, F., Bernard, L., Bonelli, L., Borgonovo, G., Bruno, W., De Cian, F., DeCensi, A., Filauro, M., and 11 others.
|
|
<strong>CDKN2A is the main susceptibility gene in Italian pancreatic cancer families.</strong>
|
|
J. Med. Genet. 49: 164-170, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22368299/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22368299</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22368299" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmedgenet-2011-100281" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Heaphy2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Heaphy, C. M., de Wilde, R. F., Jiao, Y., Klein, A. P., Edil, B. H., Shi, C., Bettegowda, C., Rodriguez, F. J., Eberhart, C. G., Hebbar, S., Offerhaus, G. J., McLendon, R., and 13 others.
|
|
<strong>Altered telomeres in tumors with ATRX and DAXX mutations.</strong>
|
|
Science 333: 425 only, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21719641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21719641</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21719641" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1207313" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Hruban2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hruban, R. H., Goggins, M., Parsons, J., Kern, S. E.
|
|
<strong>Progression model for pancreatic cancer.</strong>
|
|
Clin. Cancer Res. 6: 2969-2972, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10955772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10955772</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10955772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Jermusyk2021" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jermusyk, A., Zhong, J., Connelly, K. E., Gordon, N., Perera, S., Abdolalizadeh, E., Zhang, T., O'Brien, A., Hoskins, J. W., Collins, I., Eiser, D., Yuan, C., and 15 others.
|
|
<strong>A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and secretion and confers risk of pancreatic cancer.</strong>
|
|
Am. J. Hum. Genet. 108: 1852-1865, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34559995/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34559995</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34559995[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34559995" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajhg.2021.09.002" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Jiao2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jiao, Y., Shi, C., Edil, B. H., de Wilde, R. F., Klimstra, D. S., Maitra, A., Schulick, R. D., Tang, L. H., Wolfgang, C. L., Choti, M. A., Velculescu, V. E., Diaz, L. A., Jr., Vogelstein, B., Kinzler, K. W., Hruban, R. H., Papadopoulos, N.
|
|
<strong>DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.</strong>
|
|
Science 331: 1199-1203, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21252315/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21252315</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21252315" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1200609" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Jones2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., Hong, S.-M., Fu, B., and 24 others.
|
|
<strong>Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.</strong>
|
|
Science 321: 1801-1806, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18772397/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18772397</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18772397[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18772397" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1164368" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Liu2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liu, C., Karam, R., Zhou, Y., Su, F., Ji, Y., Li, G., Xu, G., Lu, L., Wang, C., Song, M., Zhu, J., Wang, Y., Zhao, Y., Foo, W. C., Zuo, M., Valasek, M. A., Javle, M., Wilkinson, M. F., Lu, Y.
|
|
<strong>The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma.</strong>
|
|
Nature Med. 20: 596-598, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24859531/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24859531</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24859531[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24859531" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nm.3548" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Liu1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Liu, Q., Yan, Y.-X., McClure, M., Nakagawa, H., Fujimura, F., Rustgi, A. K.
|
|
<strong>MTS-1 (CDKN2) tumor suppressor gene deletions are a frequent event in esophagus squamous cancer and pancreatic adenocarcinoma cell lines.</strong>
|
|
Oncogene 10: 619-622, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7845688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7845688</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7845688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Lowenfels1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lowenfels, A. B., Maisonneuve, P., DiMagno, E. P., Elitsur, Y., Gates, L. K., Jr., Perrault, J., Whitcomb, D. C., The International Hereditary Pancreatitis Study Group.
|
|
<strong>Hereditary pancreatitis and the risk of pancreatic cancer.</strong>
|
|
J. Nat. Cancer Inst. 89: 442-446, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9091646/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9091646</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9091646" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/jnci/89.6.442" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Lynch1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lynch, H. T., Fusaro,L., Smyrk, T. C., Watson, P., Lanspa, S., Lynch, J. F.
|
|
<strong>Medical genetic study of eight pancreatic cancer-prone families.</strong>
|
|
Cancer Invest. 13: 141-149, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7874567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7874567</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7874567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3109/07357909509011683" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="MacDermott1973" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
MacDermott, R. P., Kramer, P.
|
|
<strong>Adenocarcinoma of the pancreas in 4 siblings.</strong>
|
|
Gastroenterology 65: 137-139, 1973.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4720820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4720820</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4720820" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="McWilliams2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
McWilliams, R. R., Rabe, K. G., Olswold, C., De Andrade, M., Petersen, G. M.
|
|
<strong>Risk of malignancy in first-degree relatives of patients with pancreatic carcinoma.</strong>
|
|
Cancer 104: 388-394, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15912495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15912495</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15912495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/cncr.21166" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Melo2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Melo, S. A., Luecke, L. B., Kahlert, C., Fernandez, A. F., Gammon, S. T., Kaye, J., LeBleu, V. S., Mittendorf, E. A., Weitz, J., Rahbari, N., Reissfelder, C., Pilarsky, C., Fraga, M. F., Piwnica-Worms, D., Kalluri, R.
|
|
<strong>Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.</strong>
|
|
Nature 523: 177-182, 2015. Note: Erratum: Nature 610: E15-E17, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26106858/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26106858</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26106858[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26106858" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature14581" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Notta2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Notta, F., Chan-Seng-Yue, M., Lemire, M., Li, Y., Wilson, G. W., Connor, A. A., Denroche, R. E., Liang, S.-B., Brown, A. M. K., Kim, J. C., Wang, T., Simpson, J. T., and 34 others.
|
|
<strong>A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns.</strong>
|
|
Nature 538: 378-382, 2016. Note: Erratum: Nature 542: 124 only, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27732578/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27732578</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27732578[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27732578" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature19823" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Olive2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., Frese, K. K., DeNicola, G., and 25 others.
|
|
<strong>Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer.</strong>
|
|
Science 324: 1457-1461, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19460966/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19460966</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19460966[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19460966" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1171362" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Perera2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Perera, R. M., Stoykova, S., Nicolay, B. N., Ross, K. N., Fitamant, J., Boukhali, M., Lengrand, J., Deshpande, V., Selig, M. K., Ferrone, C. R., Settleman, J., Stephanopoulos, G., Dyson, N. J., Zoncu, R., Ramaswamy, S., Haas, W., Bardeesy, N.
|
|
<strong>Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism.</strong>
|
|
Nature 524: 361-365, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168401/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168401</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168401[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26168401" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature14587" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Petersen2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Petersen, G. M., Amundadottir, L., Fuchs, C. S., Kraft, P., Stolzenberg-Solomon, R. Z., Jacobs, K. B., Arslan, A. A., Bueno-de-Mesquita, H. B., Gallinger, S., Gross, M., Helzlsouer, K., Holly, E. A., and 61 others.
|
|
<strong>A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.</strong>
|
|
Nature Genet. 42: 224-228, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20101243/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20101243</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20101243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng.522" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Reimer1977" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reimer, R. R., Fraumeni, J. F., Jr., Ozols, R. F., Bender, R.
|
|
<strong>Pancreatic cancer in father and son. (Letter)</strong>
|
|
Lancet 309: 911 only, 1977. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/67325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">67325</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=67325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0140-6736(77)91244-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Rosenfeldt2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rosenfeldt, M. T., O'Prey, J., Morton, J. P., Nixon, C., MacKay, G., Mrowinska, A., Au, A., Rai, T. S., Zheng, L., Ridgway, R., Adams, P. D., Anderson, K. I., Gottlieb, E., Sansom, O. J., Ryan, K. M.
|
|
<strong>p53 status determines the role of autophagy in pancreatic tumour development.</strong>
|
|
Nature 504: 296-300, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24305049/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24305049</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24305049" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature12865" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Seifert2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Seifert, L., Werba, G., Tiwari, S., Giao Ly, N. N., Alothman, S., Alqunaibit, D., Avanzi, A., Barilla, R., Daley, D., Greco, S. H., Torres-Hernandez, A., Pergamo, M., and 10 others.
|
|
<strong>The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.</strong>
|
|
Nature 532: 245-249, 2016. Note: Erratum: Nature 591: E28, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27049944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27049944</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27049944[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27049944" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature17403" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Shi2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shi, Y., Gao, W., Lytle, N. K., Huang, P., Yuan, X., Dann, A. M., Ridinger-Saison, M., DelGiorno, K. E., Antal, C. E., Liang, G., Atkins, A. R., Erikson, G., and 25 others.
|
|
<strong>Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.</strong>
|
|
Nature 569: 131-135, 2019. Note: Erratum: Nature 600: E18, 2021.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30996350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30996350</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30996350[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30996350" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/s41586-019-1130-6" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Son2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., Kang, Y., Fleming, J. B., Bardeesy, N., Asara, J. M., Haigis, M. C., DePinho, R. A., Cantley, L. C., Kimmelman, A. C.
|
|
<strong>Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway.</strong>
|
|
Nature 496: 101-105, 2013. Note: Erratum: Nature 499: 504 only, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23535601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23535601</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23535601[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23535601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature12040" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Swift1976" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Swift, M., Sholman, L., Perry, M., Chase, C.
|
|
<strong>Malignant neoplasms in the families of patients with ataxia-telangiectasia.</strong>
|
|
Cancer Res. 36: 209-215, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1248000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1248000</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1248000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Thayer2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Thayer, S. P., di Magliano, M. P., Heiser, P. W., Nielsen, C. M., Roberts, D. J., Lauwers, G. Y., Qi, Y. P., Gysin, S., Fernandez-del Castillo, C., Yajnik, V., Antoniu, B., McMahon, M., Warshaw, A. L., Hebrok, M.
|
|
<strong>Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis.</strong>
|
|
Nature 425: 851-856, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14520413/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14520413</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14520413[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14520413" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature02009" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Waddell2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., Quek, K., Quinn, M. C. J., Robertson, A. J., and 78 others.
|
|
<strong>Whole genomes redefine the mutational landscape of pancreatic cancer.</strong>
|
|
Nature 518: 495-501, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25719666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25719666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25719666[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25719666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature14169" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Whelan1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Whelan, A. J., Bartsch, D., Goodfellow, P. J.
|
|
<strong>Brief report: a familial syndrome of pancreatic cancer and melanoma with a mutation in the CDKN2 tumor-suppressor gene.</strong>
|
|
New Eng. J. Med. 333: 975-977, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7666917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7666917</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7666917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM199510123331505" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Yachida2010" class="mim-anchor"></a>
|
|
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|
|
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|
|
Yachida, S., Jones, S., Bozic, I., Antal, T., Leary, R., Fu, B., Kamiyama, M., Hruban, R. H., Eshleman, J. R., Nowak, M. A., Velculescu, V. E., Kinzler, K. W., Vogelstein, B., Iacobuzio-Donahue, C. A.
|
|
<strong>Distant metastasis occurs late during the genetic evolution of pancreatic cancer.</strong>
|
|
Nature 467: 1114-1117, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20981102/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20981102</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20981102[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20981102" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature09515" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Yamamoto2020" class="mim-anchor"></a>
|
|
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|
|
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|
|
Yamamoto, K., Venida, A., Yano, J., Biancur, D. E., Kakiuchi, M., Gupta, S., Sohn, A. S. W., Mukhopadhyay, S., Lin, E. Y., Parker, S. J., Banh, R. S., Paulo, J. A., Wen, K. W., Debnath, J., Kim, G. E., Mancias, J. D., Fearon, D. T., Perera, R. M., Kimmelman, A. C.
|
|
<strong>Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I.</strong>
|
|
Nature 581: 100-105, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32376951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32376951</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32376951[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32376951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1038/s41586-020-2229-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
|
<a id="Yao2019" class="mim-anchor"></a>
|
|
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|
|
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|
|
Yao, W., Rose, J. L., Wang, W., Seth, S., Jiang, H., Taguchi, A., Liu, J., Yan, L., Kapoor, A., Hou, P., Chen, Z., Wang, Q., and 26 others.
|
|
<strong>Syndecan 1 is a critical mediator of macropinocytosis in pancreatic cancer.</strong>
|
|
Nature 568: 410-414, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30918400/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30918400</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30918400[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30918400" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
|
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[<a href="https://doi.org/10.1038/s41586-019-1062-1" target="_blank">Full Text</a>]
|
|
|
|
|
|
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|
|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
|
Zhen, D. B., Rabe, K. G., Gallinger, S., Syngal, S., Schwartz, A. G., Goggins, M. G., Hruban, R. H., Cote, M. L., McWilliams, R. R., Roberts, N. J., Cannon-Albright, L. A., Li, D., Moyes, K., Wenstrup, R. J., Hartman, A.-R., Seminara, D., Klein, A. P., Petersen, G. M.
|
|
<strong>BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study.</strong>
|
|
Genet. Med. 17: 569-577, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25356972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25356972</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25356972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/gim.2014.153" target="_blank">Full Text</a>]
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Zheng, J., Huang, X., Tan, W., Yu, D., Du, Z., Chang, J., Wei, L., Han, Y., Wang, C., Che, X., Zhou, Y., Miao, X., and 12 others.
|
|
<strong>Pancreatic cancer risk variant in LINC00673 creates a miR-1231 binding site and interferes with PTPN11 degradation.</strong>
|
|
Nature Genet. 48: 747-757, 2016.
|
|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27213290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27213290</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27213290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.3568" target="_blank">Full Text</a>]
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Bao Lige - updated : 11/15/2021
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Ada Hamosh - updated : 09/16/2020<br>Ada Hamosh - updated : 09/08/2020<br>Ada Hamosh - updated : 03/27/2020<br>Ada Hamosh - updated : 12/18/2019<br>Ada Hamosh - updated : 09/19/2019<br>Ada Hamosh - updated : 09/12/2019<br>Ada Hamosh - updated : 08/27/2019<br>Ada Hamosh - updated : 01/19/2018<br>Ada Hamosh - updated : 09/30/2016<br>Patricia A. Hartz - updated : 08/16/2016<br>Ada Hamosh - updated : 02/03/2016<br>Ada Hamosh - updated : 10/19/2015<br>Ada Hamosh - updated : 9/24/2015<br>Ada Hamosh - updated : 9/11/2015<br>Ada Hamosh - updated : 8/29/2014<br>Ada Hamosh - updated : 1/13/2014<br>Ada Hamosh - updated : 5/30/2013<br>Ada Hamosh - updated : 12/14/2012<br>Cassandra L. Kniffin - updated : 4/10/2012<br>Ada Hamosh - updated : 9/2/2011<br>Ada Hamosh - updated : 6/6/2011<br>Ada Hamosh - updated : 4/8/2011<br>Ada Hamosh - updated : 2/15/2011<br>Ada Hamosh - updated : 6/18/2010<br>Anne M. Stumpf - reorganized : 4/9/2010<br>Ada Hamosh - updated : 11/10/2009<br>Ada Hamosh - updated : 7/9/2009<br>Ada Hamosh - updated : 6/16/2009<br>Cassandra L. Kniffin - updated : 3/30/2009<br>Ada Hamosh - updated : 10/20/2008<br>Matthew B. Gross - reorganized : 9/8/2008<br>Marla J. F. O'Neill - updated : 10/6/2005<br>Ada Hamosh - updated : 9/25/2003<br>Victor A. McKusick - updated : 9/19/2002<br>Victor A. McKusick - updated : 8/15/2002<br>Victor A. McKusick - updated : 4/12/2002<br>Victor A. McKusick - updated : 2/25/2002<br>Victor A. McKusick - updated : 11/30/1998<br>Clair A. Francomano - updated : 5/15/1995
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Victor A. McKusick : 6/4/1986
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alopez : 07/15/2022<br>carol : 02/14/2022<br>mgross : 11/15/2021<br>carol : 04/23/2021<br>carol : 09/17/2020<br>alopez : 09/16/2020<br>alopez : 09/08/2020<br>alopez : 03/27/2020<br>alopez : 12/18/2019<br>alopez : 11/26/2019<br>alopez : 09/19/2019<br>alopez : 09/12/2019<br>alopez : 08/27/2019<br>alopez : 01/19/2018<br>alopez : 09/30/2016<br>mgross : 08/16/2016<br>alopez : 02/03/2016<br>alopez : 10/19/2015<br>alopez : 9/24/2015<br>alopez : 9/11/2015<br>alopez : 8/29/2014<br>alopez : 1/13/2014<br>alopez : 10/1/2013<br>alopez : 5/30/2013<br>alopez : 12/18/2012<br>alopez : 12/17/2012<br>terry : 12/14/2012<br>terry : 9/17/2012<br>alopez : 4/10/2012<br>alopez : 3/8/2012<br>alopez : 3/7/2012<br>mgross : 10/31/2011<br>alopez : 9/2/2011<br>terry : 9/2/2011<br>alopez : 6/14/2011<br>terry : 6/6/2011<br>alopez : 4/11/2011<br>terry : 4/8/2011<br>alopez : 2/18/2011<br>terry : 2/15/2011<br>alopez : 9/23/2010<br>terry : 9/21/2010<br>alopez : 6/29/2010<br>terry : 6/18/2010<br>terry : 6/18/2010<br>alopez : 5/25/2010<br>alopez : 4/27/2010<br>alopez : 4/15/2010<br>alopez : 4/9/2010<br>alopez : 4/8/2010<br>alopez : 11/12/2009<br>terry : 11/10/2009<br>alopez : 7/16/2009<br>terry : 7/9/2009<br>alopez : 6/23/2009<br>terry : 6/16/2009<br>wwang : 4/10/2009<br>ckniffin : 3/30/2009<br>terry : 3/13/2009<br>alopez : 10/22/2008<br>terry : 10/20/2008<br>mgross : 9/8/2008<br>wwang : 10/12/2005<br>terry : 10/6/2005<br>mgross : 4/13/2005<br>alopez : 10/31/2003<br>tkritzer : 10/1/2003<br>terry : 9/25/2003<br>terry : 2/26/2003<br>terry : 12/17/2002<br>tkritzer : 9/25/2002<br>tkritzer : 9/24/2002<br>carol : 9/19/2002<br>carol : 9/19/2002<br>tkritzer : 8/21/2002<br>tkritzer : 8/19/2002<br>terry : 8/15/2002<br>alopez : 4/16/2002<br>terry : 4/12/2002<br>mgross : 2/26/2002<br>terry : 2/25/2002<br>carol : 4/3/2001<br>carol : 6/12/1999<br>carol : 5/24/1999<br>carol : 11/30/1998<br>mark : 4/9/1996<br>mark : 12/8/1995<br>terry : 12/8/1995<br>terry : 7/28/1995<br>mark : 7/24/1995<br>davew : 6/6/1994<br>mimadm : 3/11/1994<br>supermim : 3/17/1992
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<h3>
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<span class="mim-font">
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<strong>#</strong> 260350
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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PANCREATIC CANCER
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</span>
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</h3>
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</div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</p>
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<h4>
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<span class="mim-font">
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PANCREATIC CARCINOMA<br />
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PANCREATIC ACINAR CARCINOMA
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</h4>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 372142002;
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<strong>ORPHA:</strong> 1333;
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<strong>DO:</strong> 4905;
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</span>
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</p>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<span class="mim-font">
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12p12.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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Pancreatic carcinoma, somatic
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</span>
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</td>
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<td>
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<span class="mim-font">
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260350
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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KRAS
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</span>
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</td>
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<td>
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<span class="mim-font">
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190070
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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12q13.13
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</span>
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</td>
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<td>
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<span class="mim-font">
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Pancreatic cancer, somatic
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</span>
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</td>
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<td>
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<span class="mim-font">
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260350
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</td>
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<td>
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<span class="mim-font">
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ACVR1B
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</span>
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</td>
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<td>
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<span class="mim-font">
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601300
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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17p13.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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Pancreatic cancer, somatic
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</span>
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</td>
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<td>
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<span class="mim-font">
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260350
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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<td>
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<span class="mim-font">
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TP53
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</td>
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<td>
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<span class="mim-font">
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191170
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</td>
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</tr>
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<tr>
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<span class="mim-font">
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18q21.2
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</span>
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</td>
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<td>
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<span class="mim-font">
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Pancreatic cancer, somatic
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</span>
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</td>
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<td>
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<span class="mim-font">
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260350
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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SMAD4
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</span>
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</td>
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<td>
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<span class="mim-font">
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600993
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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19p13.3
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</span>
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</td>
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<td>
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<span class="mim-font">
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Pancreatic cancer, somatic
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</span>
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</td>
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<td>
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<span class="mim-font">
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260350
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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STK11
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</span>
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</td>
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<td>
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<span class="mim-font">
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602216
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because mutations in a number of genes are associated with pancreatic carcinoma, familial or sporadic, germline or somatic.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Pancreatic cancer shows among the highest mortality rates of any cancer, with a 5-year relative survival rate of less than 5%. By the time of initial diagnosis, metastatic disease is commonly present. Established risk factors include a family history of pancreatic cancer, a medical history of diabetes type 2, and cigarette smoking (summary by Amundadottir et al., 2009). </p><p><strong><em>Genetic Heterogeneity of Pancreatic Cancer</em></strong></p><p>
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Somatic mutations in pancreatic cancer occur in the KRAS (190070), CDKN2A (600160), MADH4 (600993), TP53 (191170), ARMET (601916), STK11 (602216), ACVR1B (601300), and RBBP8 (604124) genes.</p><p>Susceptibility loci for pancreatic cancer include PNCA1 (606856), related to mutation in the PALLD gene on chromosome 4q32 (608092); PNCA2 (613347), related to mutation in the BRCA2 gene on chromosome 13q12 (600185); PNCA3 (613348), related to mutation in the PALB2 gene on chromosome 16p12 (610355); PNCA4 (614320), related to mutation in the BRCA1 gene on chromosome 17q21 (113705); and PNCA5 (618680), related to mutation in the RABL3 gene on chromosome 3q13 (618542).</p><p><strong><em>Occurrence of Pancreatic Cancer in Other Disorders</em></strong></p><p>
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Several familial cancer syndromes increase the risk of pancreatic cancer. The best characterized include hereditary nonpolyposis colon cancer syndrome (HNPCC; see 120435); hereditary breast-ovarian cancer syndrome due to mutations in BRCA2; Peutz-Jeghers syndrome (175200); the melanoma-pancreatic cancer syndrome (606719), caused by mutations in CDKN2A (600160); von Hippel-Lindau syndrome (193300), ataxia-telangiectasia (208900) (Swift et al., 1976), and juvenile polyposis syndrome (174900). </p><p>Patients with hereditary pancreatitis (167800) resulting from gain-of-function mutations in the protease serine-1 gene (PRSS1; 276000) have a lifetime pancreatic cancer risk ratio of 57 and a cumulative incidence, to age 70 years, of 40% (Lowenfels et al., 1997). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Friedman and Fialkow (1976) observed cancer of the pancreas in 4 brothers from a sibship of 6. Diagnosis was made between ages 66 and 75 years. None had a history of pancreatitis or tumors at other sites. </p><p>Reimer et al. (1977) reported pancreatic cancer in father and son. </p><p>In a family of European Jewish ancestry, Ehrenthal et al. (1987) identified pancreatic adenocarcinoma in women of 3 successive generations. The diagnosis was histologically confirmed in each case. The youngest of the 3 women presented at age 29, her mother at age 42, and her grandmother at age 76. </p><p>Lynch et al. (1995) studied 8 families in which 2 or more first-degree relatives had pancreatic cancer. In the 8 families, 25 pancreatic cancers were found. The mean age of occurrence was 62.8 years, with a range from 45 to 90 years. Parent and child occurrence was observed in 4 of the 8 families. In one family, the progenitor had an affected brother and 5 of his 8 children developed cancer; 2 had pancreatic cancer, 2 had breast cancer (one of these also had pancreatic cancer), and 1 daughter had ovarian cancer. Of the 7 carcinomas available for pathologic review, 6 were typical ductal adenocarcinomas and the seventh was a giant cell variant of ductal carcinoma. </p><p>Caldas et al. (1994) quoted Boring et al. (1993) as indicating that pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death in either sex in the United States, with an estimated incidence in 1993 of nearly 27,700 and a mortality of 24,500. </p><p>Evans et al. (1995) described a large pedigree in which pancreatic cancer was inherited as an autosomal dominant. Diabetes and exocrine insufficiency were observed in all family members who eventually developed pancreatic cancer. The presence of diabetes, often years before the diagnosis of cancer, allowed identification of those people who had inherited the predisposing allele. The lack of attacks of abdominal pain seemingly distinguishes the affected members of this family from hereditary pancreatitis (167800) in which diabetes mellitus and pancreatic cancer occur, but the distinction is by no means clear because it was stated that 6 of the 9 persons who developed pancreatic cancer in this family also had a history clinically compatible with pancreatic insufficiency before diagnosis of cancer: weight loss, fatty and foul smelling stools, increased fecal fat, and relief with exogenous pancreatic enzyme supplementation. All 9 members of the family with pancreatic cancer were males. </p><p>Making use of pathologic, clinical, and genetic knowledge, Hruban et al. (2000) composed a progression model of pancreatic carcinoma, similar to that developed for colorectal carcinoma. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Management</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Because CD40 (109535) activation can reverse immune suppression and drive antitumor T cell responses, Beatty et al. (2011) tested the combination of an agonist CD40 antibody with gemcitabine chemotherapy in a small cohort of patients with surgically incurable pancreatic ductal adenocarcinoma (PDA) and observed tumor regressions in some patients. They reproduced this treatment effect in a genetically engineered mouse model of PDA and found unexpectedly that tumor regression required macrophages but not T cells or gemcitabine. CD40-activated macrophages rapidly infiltrated tumors, became tumoricidal, and facilitated the depletion of tumor stroma. Thus, Beatty et al. (2011) concluded that cancer immune surveillance does not necessarily depend on therapy-induced T cells; rather, their findings demonstrated a CD40-dependent mechanism for targeting tumor stroma in the treatment of cancer. </p><p>The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of SMAD4 (600993). As loss of neighboring housekeeping genes can confer collateral lethality, Dey et al. (2017) sought to determine whether loss of the metabolic gene malic enzyme-2 (ME2; 154270) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3 (604626). Dey et al. (2017) showed that ME3 depletion selectively kills ME2-null PDAC cells in a manner consistent with an essential function for ME3 in ME2-null cancer cells. Mechanistically, integrated metabolomic and molecular investigation of cells deficient in mitochondrial malic enzymes revealed diminished NADPH production and consequent high levels of reactive oxygen species. These changes activate AMP-activated protein kinase (AMPK; see 602739), which in turn directly suppresses sterol regulatory element-binding protein-1 (SREBP1; 184756)-directed transcription of its direct targets, including the branched-chain amino acid transaminase-2 gene BCAT2 (113530). BCAT2 catalyses the transfer of the amino group from branched-chain amino acids to alpha-ketoglutarate, thereby regenerating glutamate, which functions in part to support de novo nucleotide synthesis. Thus, mitochondrial malic enzyme deficiency, which results in impaired NADPH production, provides a prime 'collateral lethality' therapeutic strategy for the treatment of a substantial fraction of patients diagnosed with intractable pancreatic cancer. </p><p>Starting with a systematic proteomic investigation of secreted pancreatic cancer disease mediators and underlying molecular mechanisms, Shi et al. (2019) revealed that leukemia inhibitory factor (LIF; 159540) is a key paracrine factor from activated pancreatic stellate cells acting on cancer cells. Both pharmacologic LIF blockade and genetic Lifr deletion markedly slowed tumor progression and augmented the efficacy of chemotherapy to prolong survival of pancreatic ductal adenocarcinoma mouse models, mainly by modulating cancer cell differentiation and epithelial-mesenchymal transition status. Moreover, in both mouse models and human pancreatic ductal adenocarcinoma, aberrant production of LIF in the pancreas was restricted to pathologic conditions and correlated with pancreatic ductal adenocarcinoma pathogenesis, and changes in the levels of circulating LIF correlated well with tumor response to therapy. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Banke et al. (2000) estimated that 10% or more of patients with pancreatic cancer inherit the risk in an autosomal dominant pattern. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Population Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>McWilliams et al. (2005) analyzed family history questionnaires from 426 patients with pancreatic cancer and compared the prevalence of malignancy reported in 3,355 of their first-degree relatives to population data from the Surveillance, Epidemiology, and End Results (SEER) Project, using age- and gender-adjusted incidence rates. McWilliams et al. (2005) found an increased risk of pancreatic and liver carcinoma in the first-degree relatives of probands with pancreatic cancer (1.88- and 2.7-fold, respectively); the risk for pancreatic cancer was nearly 3-fold when the proband was diagnosed before 60 years of age, but no other malignancies were increased in this subgroup. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Pathogenesis</strong>
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<p>Berman et al. (2003) demonstrated that a wide range of digestive tract tumors, including most of those originating in the esophagus, stomach, biliary tract, and pancreas, but not in the colon, display increased hedgehog pathway activity, which is suppressible by cyclopamine, a hedgehog pathway antagonist. Cyclopamine also suppresses cell growth in vitro and causes durable regression of xenograft tumors in vivo. Unlike tumors in Gorlin syndrome (109400), pathway activity and cell growth in these digestive tract tumors are driven by endogenous expression of hedgehog ligands, as indicated by the presence of Sonic hedgehog (SHH; 600725) and Indian hedgehog (IHH; 600726) transcripts, by the pathway- and growth-inhibitory activity of a hedgehog-neutralizing antibody, and by the dramatic growth-stimulatory activity of exogenously added hedgehog ligand. Berman et al. (2003) concluded that their results identified a group of common lethal malignancies in which hedgehog pathway activity, essential for tumor growth, is activated not by mutation but by ligand expression. </p><p>Thayer et al. (2003) reported that Sonic hedgehog is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions, pancreatic intraepithelial neoplasia. The pancreata of Pdx1- (600733) Shh mice (in which Sonic hedgehog is misexpressed in the pancreatic endoderm) developed abnormal tubular structures, a phenocopy of human pancreatic intraepithelial neoplasia-1 and -2. Moreover, these pancreatic intraepithelial neoplasia-like lesions also contained mutations in Kras (190070) and overexpressed Erbb2 (164870), which are genetic mutations found early in the progression of human pancreatic cancer. Furthermore, hedgehog signaling remained active in cell lines established from primary and metastatic pancreatic adenocarcinomas. Notably, inhibition of hedgehog signaling by cyclopamine induced apoptosis and blocked proliferation in a subset of the pancreatic cancer cell lines both in vitro and in vivo. Thayer et al. (2003) concluded that their data suggested that the hedgehog pathway may have an early and critical role in the genesis of pancreatic cancer, and that maintenance of hedgehog signaling is important for aberrant proliferation and tumorigenesis. </p><p>Jones et al. (2008) performed a comprehensive genetic analysis of 24 pancreatic cancers. They determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in these samples. They then searched for homozygous deletions and amplifications in the tumor DNA by using microarrays containing probes for approximately 1 million SNPs. Jones et al. (2008) found that pancreatic cancers contain an average of 63 genetic alterations, the majority of which are point mutations. These alterations defined a core set of 12 cellular signaling pathways and processes that were each genetically altered in 67 to 100% of the tumors. Analysis of these tumors' transcriptomes with next-generation sequencing-by-synthesis technologies provided independent evidence for the importance of these pathways and processes. Jones et al. (2008) concluded that genetically altered core pathways and regulatory processes only become evident once the coding regions of the genome are analyzed in depth. The authors suggested that dysregulation of these core pathways and processes through mutation can explain the major features of pancreatic tumorigenesis. The 12 signaling pathways implicated in pancreatic tumorigenesis included apoptosis, DNA damage control, regulation of the G1/S phase transition, hedgehog signaling, homophilic cell adhesion, integrin signaling, C-Jun (165160) N-terminal kinase signaling, KRAS (190070) signaling, regulation of invasion, small GTPase-dependent signaling other than KRAS, TGF-beta (190180) signaling, and WNT (see 164975)/Notch (190198) signaling. </p><p>Campbell et al. (2010) used advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. Campbell et al. (2010) found that pancreatic cancer acquires rearrangements indicative of telomere dysfunction and abnormal cell-cycle control, i.e., dysregulated G1-to-S-phase transition with intact G2-M checkpoint. These initiate amplification of cancer genes and occur predominantly in early cancer development rather than the later stages of the disease. Genomic instability frequently persists after cancer dissemination, resulting in ongoing parallel and even convergent evolution among different metastases. Campbell et al. (2010) found evidence that there is genetic heterogeneity among metastasis-initiating cells, that seeding metastasis may require driver mutations beyond those required for primary tumors, and that phylogenetic trees across metastases show organ-specific branches. Campbell et al. (2010) concluded that their data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection. </p><p>Yachida et al. (2010) used data generated by sequencing the genomes of 7 pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers and found that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, nonmetastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, nonmetastatic founder cell. At least 5 more years are required for the acquisition of metastatic ability, and patients die an average of 2 years thereafter. Yachida et al. (2010) concluded that their data provided novel insights into the genetic features underlying pancreatic cancer progression and defined a broad time window of opportunity for early detection to prevent deaths from metastatic disease. </p><p>Son et al. (2013) reported the identification of a noncanonical pathway of glutamine use in human pancreatic ductal adenocarcinoma (PDAC) cells that is required for tumor growth. Whereas most cells use glutamate dehydrogenase (GLUD1; 138130) to convert glutamine-derived glutamate into alpha-ketoglutarate in the mitochondria to fuel the tricarboxylic acid cycle, PDAC relies on a distinct pathway in which glutamine-derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase (GOT1; 138180). Subsequently, this oxaloacetate is converted into malate and then pyruvate, ostensibly increasing the NADPH/NADP+ ratio which can potentially maintain the cellular redox state. Importantly, PDAC cells are strongly dependent on this series of reactions, as glutamine deprivation or genetic inhibition of any enzyme in this pathway leads to an increase in reactive oxygen species and a reduction in reduced glutathione. Moreover, knockdown of any component enzyme in this series of reactions also results in a pronounced suppression of PDAC growth in vitro and in vivo. Furthermore, Son et al. (2013) established that the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in PDAC, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway. </p><p>In a humanized genetically modified mouse model of PDAC, Rosenfeldt et al. (2013) showed that autophagy's role in tumor development is intrinsically connected to the status of the tumor suppressor p53 (191170). Mice with pancreases containing an activated oncogenic allele of Kras, the most common mutational event in PDAC, developed a small number of precancerous lesions that stochastically developed into PDAC over time. However, mice also lacking the essential autophagy genes Atg5 (604261) or Atg7 (608760) accumulated low-grade, premalignant pancreatic intraepithelial neoplasia lesions, but progression to high-grade pancreatic intraepithelial neoplasias and PDAC was blocked. In marked contrast, in mice containing oncogenic Kras and lacking p53, loss of autophagy no longer blocked tumor progression but actually accelerated tumor onset, with metabolic analysis revealing enhanced glucose uptake and enrichment of anabolic pathways, which can fuel tumor growth. Rosenfeldt et al. (2013) also show that treatment of mice with the autophagy inhibitor hydroxychloroquine significantly accelerates tumor formation in mice containing oncogenic Kras but lacking p53. </p><p>The pathogenesis of pancreatic ductal adenocarcinoma (PDA) requires high levels of autophagy, a conserved self-degradative process. Perera et al. (2015) showed that autophagy induction in PDA occurs as part of a broader transcriptional program that coordinates activation of lysosome biogenesis and function, and nutrient scavenging, mediated by the MiT/TFE family of transcription factors. In human PDA cells, the MiT/TFE proteins (MITF, 156845; TFE3, 314310; and TFEB, 600744) are decoupled from regulatory mechanisms that control their cytoplasmic retention. Increased nuclear import in turn drives the expression of a coherent network of genes that induce high levels of lysosomal catabolic function essential for PDA growth. Unbiased global metabolite profiling revealed that MiT/TFE-dependent autophagy-lysosome activation is specifically required to maintain intracellular amino acid pools. Perera et al. (2015) concluded that their results identified the MiT/TFE proteins as master regulators of metabolic reprogramming in pancreatic cancer and demonstrated that transcriptional activation of clearance pathways converging on the lysosome is a novel hallmark of aggressive malignancy. </p><p>Seifert et al. (2016) reported that the principal components of the necrosome, receptor-interacting proteins RIP1 (603453) and RIP3 (605817), are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Cytoplasmic SF3B3 (605592), a subunit of the histone deacetylase complex, was expressed in PDA in a RIP1/RIP3-dependent manner, and MINCLE (609962), its cognate receptor, was upregulated in tumor-infiltrating myeloid cells. Ligation of MINCLE by SAP130 promoted oncogenesis, whereas deletion of MINCLE protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumor microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or MINCLE is deleted. Accordingly, T cells, which are not protective against PDA progression in mice with intact RIP3 or MINCLE signaling, were reprogrammed into indispensable mediators of antitumor immunity in the absence of RIP3 or MINCLE. Seifert et al. (2016) concluded that their work described parallel networks of necroptosis-induced CXCL1 and MINCLE signaling that promote macrophage-induced adaptive immune suppression and thereby enable PDA progression. </p><p>Bailey et al. (2016) performed integrated genomic analysis of 456 pancreatic ductal adenocarcinomas and identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-beta, WNT, NOTCH, ROBO/SLIT signaling (see 602430), G1/S transition, SWI-SNF (see 603111), chromatin modification, DNA repair, and RNA processing. Expression analysis defined 4 subtypes: (1) squamous; (2) pancreatic progenitor; (3) immunogenic; and (4) aberrantly differentiated endocrine exocrine (ADEX) that correlate with histopathologic characteristics. Squamous tumors are enriched for TP53 (191170) and KDM6A (300128) mutations, upregulation of the TP63-delta-N (603273) transcriptional network, and hypermethylation of pancreatic endodermal cell fate-determining genes, and have a poor prognosis. Pancreatic progenitor tumors preferentially express genes involved in early pancreatic development (FOXA2 (600288)/FOXA3 (602295); PDX1, 600733; and MNX1, 142994). ADEX tumors displayed upregulation of genes that regulate networks involved in KRAS activation, exocrine (NR5A2, 604453 and RBPJL, 616104), and endocrine differentiation (NEUROD1, 601724 and NKX2-2, 604612). Immunogenic tumors contained upregulated immune networks including pathways involved in acquired immune suppression. </p><p>To study the role of glycan changes in pancreatic disease, Engle et al. (2019) inducibly expressed human fucosyltransferase-3 (FUT3; 111100) and beta-1,3-galactosyltransferase-5 (B3GALT5; 604066) in mice, reconstituting the glycan sialyl-Lewis, also known as carbohydrate antigen 19-9 (CA19-9). Notably, CA19-9 expression in mice resulted in rapid and severe pancreatitis with hyperactivation of epidermal growth factor receptor (EGFR) signaling. Mechanistically, CA19-9 modification of the matricellular protein fibulin-3 (FBLN3; 601548) increased its interaction with EGFR, and blockade of fibulin-3, EGFR ligands, or CA19-9 prevented EGFR hyperactivation in organoids. CA19-9-mediated pancreatitis was reversible and could be suppressed with CA19-9 antibodies. CA19-9 also cooperated with the Kras(G12D) oncogene (190070.0003) to produce aggressive pancreatic cancer. Engle et al. (2019) concluded that their findings implicated CA19-9 in the etiology of pancreatitis and pancreatic cancer and nominated CA19-9 as a therapeutic target. </p><p>Yao et al. (2019) developed an unbiased functional target discovery platform to query oncogeneic KRAS-dependent changes of the pancreatic ductal adenocarcinoma surfaceome, which revealed syndecan-1 (SDC1; 186355) as a protein that is upregulated at the cell surface by oncogenic KRAS. Localization of SDC1 at the cell surface, where it regulates macropinocytosis, an essential metabolic pathway that fuels pancreatic ductal adenocarcinoma cell growth, is essential for disease maintenance and progression. </p><p>Notta et al. (2016) tracked changes in DNA copy number and their associated rearrangements in tumor-enriched genomes and found that pancreatic cancer tumorigenesis is neither gradual nor follows the accepted mutation order. Two-thirds of tumors analyzed harbored complex rearrangement patterns associated with mitotic errors, consistent with punctuated equilibrium as the principal evolutionary trajectory. In a subset of cases, the consequence of such errors was the simultaneous, rather than sequential, knockout of canonical preneoplastic genetic drivers that are likely to set off invasive cancer growth. Notta et al. (2016) concluded that these findings challenged the pancreatic intraepithelial neoplasm (PanIN) progression model of pancreatic cancer and provided insights into the mutational processes that give rise to these aggressive tumors. </p><p>Aykut et al. (2019) showed that fungi migrate from the gut lumen to the pancreas and that this is implicated in the pathogenesis of pancreatic ductal adenocarcinoma (PDA). PDA tumors in humans and mouse models of this cancer displayed an increase in fungi of about 3,000-fold compared to normal pancreatic tissue. The composition of the mycobiome of PDA tumors was distinct from that of the gut or normal pancreas on the basis of alpha- and beta-diversity indices. Specifically, the fungal community that infiltrated PDA tumors was markedly enriched for Malassezia species in both mice and humans. Ablation of the mycobiome was protective against tumor growth in slowly progressive and invasive models of PDA, and repopulation with a Malassezia species, but not species in the genera Candida, Saccharomyces, or Aspergillus, accelerated oncogenesis. Aykut et al. (2019) also discovered that ligation of mannose-binding lectin (MBL2; 154545), which binds to glycans of the fungal wall to activate the complement cascade, was required for oncogenic progression, whereas deletion of MBL or C3 (120700) in the extratumoral compartment, or knockdown of C3AR (605246) in tumor cells, were both protective against tumor growth. In addition, reprogramming of the mycobiome did not alter the progression of PDA in Mbl-null or C3-deficient mice. Aykut et al. (2019) concluded that their work showed that pathogenic fungi promote PDA by driving the complement cascade through the activation of MBL. </p><p>Ferroptosis is a form of cell death that results from the catastrophic accumulation of lipid ROS. Oncogenic signaling elevates lipid ROS production in many tumor types and is counteracted by metabolites that are derived from the amino acid cysteine. Badgley et al. (2020) showed that the import of oxidized cysteine (cystine) via system x(C)- is a critical dependency of PDAC. PDAC cells used cysteine to synthesize glutathione and coenzyme A, which, together, downregulate ferroptosis. Studying genetically engineered mice, Badgley et al. (2020) found that the deletion of a system x(C)- subunit, Slc7a11 (607933), induced tumor-selective ferroptosis and inhibited PDAC growth. This was replicated through the administration of cyst(e)inase, a drug that depletes cysteine and cystine, demonstrating a translatable means to induce ferroptosis in PDAC. </p><p>Yamamoto et al. (2020) showed that in PDAC, major histocompatibility complex class I (MHC-I; see 142800) molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves the receptor NBR1 (166945). PDAC cells displayed reduced expression of MHC-I at the cell surface and instead demonstrated localization in autophagosomes and lysosomes. Inhibition of autophagy restored surface levels of MHC-I and led to improved antigen presentation, enhanced antitumor T cell responses, and reduced tumor growth in syngeneic host mice. The antitumor effects of autophagy inhibition were reversed by depleting CD8+ T cells or reducing surface expression of MHC-I. Inhibition of autophagy synergized with dual immune check-point blockade therapy and led to enhanced antitumor immune response. </p><p><strong><em>Pancreatic Neuroendocrine Tumors</em></strong></p><p>
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Heaphy et al. (2011) evaluated telomere status in pancreatic neuroendocrine tumors (PanNETs) in which ATRX (300032) and DAXX (603186) mutational status had been determined through Sanger sequencing. Telomere-specific FISH revealed that 25 of 41 (61%) PanNETs displayed large, ultrabright telomere FISH signals, a nearly universal feature of the telomerase-independent telomere maintenance mechanism termed alternative lengthening of telomeres. ATRX and DAXX gene mutations both were significantly correlated with ALT positivity (P less than 0.008 for each gene). All 19 (100%) PanNETs with ATRX or DAXX gene mutations were ALT-positive, whereas 6 of 20 cases without detectable mutations were ALT-positive. To ascertain whether ATRX and DAXX gene mutations might be more generally associated with the ALT phenotype, Heaphy et al. (2011) examined 439 tumors of other types and found a strong correlation between inactivation of ATRX or DAXX and the ALT phenotype in unrelated tumor types. </p>
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<strong>Diagnosis</strong>
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<p>Using mass spectrometry analyses, Melo et al. (2015) identified a cell surface proteoglycan, glypican-1 (GPC1; 600395), specifically enriched on cancer cell-derived exosomes. GPC1-positive circulating exosomes were monitored and isolated using flow cytometry from the serum of patients and mice with cancer. GPC1-positive circulating exosomes were detected in the serum of patients with pancreatic cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreatic disease from patients with early- and late-stage pancreatic cancer. Levels of GPC1-positive circulating exosomes correlated with tumor burden and the survival of pre- and post-surgical patients. GPC1-positive circulating exosomes from patients and from mice with spontaneous pancreatic tumors carry specific KRAS (190070) mutations, and reliably detected pancreatic intraepithelial lesions in mice despite negative signals by MRI. Melo et al. (2015) concluded that GPC1-positive circulating exosomes may serve as a potential noninvasive diagnostic and screening tool to detect early stages of pancreatic cancer to facilitate possible curative surgical therapy. </p>
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<strong>Mapping</strong>
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<p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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Amundadottir et al. (2009) conducted a 2-stage genomewide association study of pancreatic cancer, genotyping over 500,000 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus 1 hospital-based case-control study. The authors conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from 8 case-control studies, adjusting for study, sex, ancestry, and 5 principal components. They identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(8); multiplicative per-allele odds ratio 1.20; 95% CI 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene (110300). The protective allele T for rs505922 is in complete linkage disequilibrium with the O allele of the ABO locus, consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B. </p><p>Petersen et al. (2010) conducted a genomewide association study of pancreatic cancer in 3,851 affected individuals and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry, and 5 principal components, Petersen et al. (2010) identified 8 SNPs that map to 3 loci on chromosomes 13q22.1, 1q32.1, and 5p15.33. Two correlated SNPs, rs9543325 (p = 3.27 x 10(-11), per-allele odds ratio 1.26, 95% CI 1.18-1.35) and rs9564966 (p = 5.86 x 10(-8), per-allele odds ratio 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2 (604453), and the strongest signal was at rs3790844 (p = 2.45 x 10(-10), per-allele odds ratio 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (p = 3.66 x 10(-7), per-allele odds ratio 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L (612585)-TERT (187270) locus on 5p15.33, which is associated with multiple cancers. Petersen et al. (2010) concluded that their study identified common susceptibility loci for pancreatic cancer that warrant follow-up studies. </p><p>By genomewide association analysis, Zheng et al. (2016) identified a G-A SNP in exon 4 of the LINC00673 gene (617079) (rs11655237) that was associated with susceptibility to pancreatic ductal adenocarcinoma in a Han Chinese population. The A allele of rs11655237 was predicted to change the local structure of LINC00673 and to introduce a potential binding site for microRNA-1231 (MIR1231; 617040). Reporter gene assays confirmed that MIR1231 inhibited expression of LINC00673 with the A allele of rs11655237 in a dose-dependent manner, but it had no effect on LINC00673 with the G allele of rs11655237. Allele-specific targeting of LINC00673 by MIR1231 inhibited LINC00673 regulation of the PTPN11 (176876) pathway, thereby promoting tumor cell growth in individuals carrying the A allele of rs11655237. </p>
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<strong>Molecular Genetics</strong>
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<p><strong><em>Mutation in KRAS2</em></strong></p><p>
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Point mutations in codon 12 of the KRAS2 gene (190070) occur in 75 to 90% of pancreatic cancers (Almoguera et al., 1988), and also occur in foci of pancreatic intraepithelial neoplasia, a putative precursor lesion of pancreatic cancer (Hruban et al., 2000). Evans et al. (1995) analyzed this gene in pancreatic tumors from patients in a large pedigree with autosomal dominant pancreatic cancer preceded by diabetes and exocrine insufficiency. The presence of diabetes, often years before the diagnosis of cancer, allowed identification of those who had inherited the predisposing allele. Pancreatic tissue from all 3 persons analyzed showed KRAS point mutations, and in all 3 the mutations were located in codon 13. The observation of several different KRAS mutations in pancreatic tumors from this family and the presence of only wildtype KRAS in normal tissue clearly showed that the mutant KRAS gene was not the germline event underlying pancreatic cancer in this family. </p><p><strong><em>Mutation in CDKN2A</em></strong></p><p>
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Although KRAS mutations are found in 85% or more of cases of pancreatic adenocarcinoma, and p53 mutations (191170) in at least of 50% of cases, little is known of the genetic changes that occur in pancreatic carcinogenesis. Caldas et al. (1994) described experiments suggesting that mutation in the p16 gene (CDKN2A; 600160), which they referred to as MTS1, is a frequent cause of pancreatic adenocarcinoma. </p><p>Liu et al. (1995) found that 50% of pancreatic cancer cell lines had deletions of both exons 1 and 2 of the CDKN2 gene; furthermore, an additional 30% of pancreatic cancer cell lines harbored point mutations or microdeletions based on DNA sequencing. </p><p>Further evidence of the role of CDKN2 in pancreatic tumorigenesis was provided by Whelan et al. (1995), who described a kindred with an increased risk of pancreatic cancers, melanomas, and possibly additional types of tumors cosegregating with a CDKN2 mutation (600160.0005). </p><p>In a population-based study, Ghiorzo et al. (2012) identified CDKN2A mutations in 13 (5.7%) of 225 Italian patients with pancreatic cancer. Six patients carried the common G101W mutation (600160.0005), which was the most common mutation. Among the 16 probands with a family history of cancer, including pancreatic cancer and melanoma, 5 (31%) were found to carry CDKN2A mutations. The mutation frequency ranged from 20% in families with 2 affected members to 50% in families with 3 affected members. The findings suggested that CDKN2A is the main susceptibility gene in Italian families with pancreatic cancer. </p><p><strong><em>Mutation in BRCA2</em></strong></p><p>
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See 613347 for information on pancreatic cancer susceptibility due to mutation in the BRCA2 gene (600185).</p><p><strong><em>Mutation in PALLD</em></strong></p><p>
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See 606856 for information on autosomal dominant pancreatic cancer due to mutation in the PALLD gene (608092).</p><p><strong><em>Mutation in PALB2</em></strong></p><p>
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See 606856 for information on pancreatic cancer susceptibility due to mutation in the PALB2 gene (610355).</p><p><strong><em>Mutation in BRCA1</em></strong></p><p>
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Al-Sukhni et al. (2008) found loss of heterozygosity at the BRCA1 locus (113705) in pancreatic tumor DNA from 5 (71%) of 7 patients with pancreatic cancer who carried a heterozygous germline BRCA1 mutation (see, e.g., 113705.0003 and 113705.0018). Pancreatic tumor DNA was available for sequencing in 4 cases, and 3 demonstrated loss of the wildtype allele. In contrast, only 1 (11%) of 9 patients with sporadic pancreatic cancer and no germline BRCA1 mutations showed LOH at the BRCA1 locus. Al-Sukhni et al. (2008) concluded that BRCA1 germline mutations likely predispose to the development of pancreatic cancer, and suggested that individuals with these mutations be considered for pancreatic cancer-screening programs. </p><p><strong><em>Mutation in Axon Guidance Pathway Genes</em></strong></p><p>
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Biankin et al. (2012) performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort of 142 patients with early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumors identified substantial heterogeneity with 2,016 nonsilent mutations and 1,628 copy number variations. Biankin et al. (2012) defined 16 significantly mutated genes, reaffirming known mutations (KRAS, 190070; TP53, 191170; CDKN2A, 600160; SMAD4, 600993; MLL3, 606833; TGFBR2, 190182; ARID1A, 603024; and SF3B1, 605590), and uncovered novel mutated genes including additional genes involved in chromatin modification (EPC1, 610999 and ARID2, 609539), DNA damage repair (ATM; 607585), and other mechanisms (ZIM2 (see 601483); MAP2K4, 601335; NALCN, 611549; SLC16A4, 603878; and MAGEA6, 300176). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signaling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. Biankin et al. (2012) also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO (see 603742) signaling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis. </p><p><strong><em>Mutation in UPF1</em></strong></p><p>
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Liu et al. (2014) identified mutations in the UPF1 gene (601430) in pancreatic adenosquamous carcinoma (ASC) tumors from 18 of 23 patients. Liu et al. (2014) also tested 3 other nonsense-mediated RNA decay (NMD) genes--UPF2 (605529), UPF3A (605530), and UPF3B (300298)--but did not detect mutations. The UPF1 mutations were somatic in origin, as they were not present in matched normal pancreatic tissues from the 18 patients. UPF1 mutations were also not detectable in 29 non-ASC pancreatic tumors and in 21 lung squamous cell carcinomas that were tested. Liu et al. (2014) concluded that UPF1 mutations are a unique signature of most pancreatic adenosquamous carcinomas. </p><p><strong><em>Multigene Studies</em></strong></p><p>
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Zhen et al. (2015) tested germline DNA from 727 unrelated probands with pancreatic cancer and a positive family history for mutations in BRCA1 (113705) and BRCA2 (600185) (including deletions and rearrangements), PALB2 (610355), and CDKN2A (600160). Among these probands, 521 met criteria for familial pancreatic cancer (FPC; at least 2 affected first-degree relatives). The prevalence of deleterious mutations, excluding variants of unknown significance, among FPC probands was BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. FPC probands carried more mutations in the 4 genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%; OR = 2.40, 95% CI 1.06-5.44, p = 0.03). The probability of testing positive for deleterious mutations in any of the 4 genes ranged up to 10.4%, depending on family history of cancers. </p><p>Waddell et al. (2015) performed whole-genome sequencing and copy number variation analysis of 100 pancreatic ductal adenocarcinomas. Chromosomal rearrangements leading to gene disruption were prevalent, affecting genes known to be important in pancreatic cancer (TP53, SMAD4, CDKN2A, ARID1A, and ROBO2, 602431) and new candidate drivers of pancreatic carcinogenesis (KDM6A, 300128 and PREX2, 612139). Patterns of structural variation classified pancreatic ductal adenocarcinomas into 4 subtypes with potential clinical utility: the subtypes were termed stable, locally rearranged, scattered, and unstable. A significant proportion harbored focal amplifications, many of which contained druggable oncogenes but at low individual patient prevalence. Genomic instability cosegregated with inactivation of DNA maintenance genes (BRCA1, BRCA2, or PALB2) and a mutational signature of DNA damage repair deficiency. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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Using data from genomewide association studies (GWAS) of 9,013 affected individuals and 12,452 control individuals of European ancestry, Jermusyk et al. (2021) fine-mapped a pancreatic cancer risk locus on chromosome 16q23.1 and identified a region containing the SNP rs72802365 as a candidate locus. A 584-bp deletion variant in the region deleted exon 6 of CTRB2 (619620), resulting in a truncated 166-amino acid protein lacking the C chain of full-length CTRB2, including 1 of 3 amino acids in the catalytic triad, ser213. Functional characterization revealed that the truncated CTRB2 protein lost chymotrypsin activity, was not secreted, and accumulated intracellularly in the endoplasmic reticulum (ER). Differential expression analysis showed that ER stress pathways were upregulated in pancreatic tissue from carriers of the CTRB2 variant, leading to increased levels of ER stress and altered translational activity in pancreas. Fluorescence-tagged truncated CTRB2 protein was retained in the ER, resulting in increased expression of ER pathway-related genes in transfected pancreatic cells, leading to ER stress. </p><p><strong><em>Pancreatic Neuroendocrine Tumors</em></strong></p><p>
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Jiao et al. (2011) explored the genetic basis of pancreatic neuroendocrine tumors (PanNETs) by determining the exomic sequence of 10 nonfamilial PanNETs and then screened the most commonly mutated genes in 58 additional PanNETs. The most frequently mutated genes specify proteins implicated in chromatin remodeling: 44% of the tumors had somatic inactivating mutations in MEN1 (613733), and 43% had mutations in genes encoding either of the 2 subunits of a transcription/chromatin remodeling complex consisting of DAXX (death domain-associated protein, 603186) and ATRX (300032). Clinically, mutations in the MEN1 and DAXX/ATRX genes were associated with better prognosis. Jiao et al. (2011) also found mutations in genes in the mTOR (601231) pathway in 14% of the tumors, a finding that could potentially be used to stratify patients for treatments with mTOR inhibitors. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>History</strong>
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</span>
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<span class="mim-text-font">
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<p>When Billy Carter, brother of President Jimmy Carter, died of pancreatic cancer in 1988, the news media reported that his sister Ruth Carter Stapleton, evangelist and faith healer, had died of pancreatic cancer at age 54 and their mother of pancreatic, bone, and breast cancer at age 85. In the New York Times of December 1, 1989, it was announced that President Carter's last surviving sib, Gloria Carter Spann, was found to be suffering from pancreatic cancer, 'the same disease that killed their father, sister and brother and contributed to the death of their mother.' The possibility of environmental causation might be raised, e.g., an agricultural insecticide or an oncogenic agent such as aflatoxin.</p>
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</span>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Olive et al. (2009) studied a mouse model of pancreatic ductal adenocarcinoma (PDA) that is refractory to the clinically used drug gemcitabine, and found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. Olive et al. (2009) tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibition of the Hedgehog cellular signaling pathway. The combination of therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. Olive et al. (2009) concluded that inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer. </p>
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</span>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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MacDermott and Kramer (1973)
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Al-Sukhni, W., Rothenmund, H., Eppel Borgida, A., Zogopoulos, G., O'Shea, A.-M., Pollett, A., Gallinger, S.
|
|
<strong>Germline BRCA1 mutations predispose to pancreatic adenocarcinoma.</strong>
|
|
Hum. Genet. 124: 271-278, 2008.
|
|
|
|
|
|
[PubMed: 18762988]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00439-008-0554-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Almoguera, C., Shibata, D., Forrester, K., Martin, J., Arnheim, N., Perucho, M.
|
|
<strong>Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes.</strong>
|
|
Cell 53: 549-554, 1988.
|
|
|
|
|
|
[PubMed: 2453289]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(88)90571-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Amundadottir, L., Kraft, P., Stolzenberg-Solomon, R. Z., Fuchs, C. S., Petersen, G. M., Arslan, A. A., Bueno-de-Mesquita, H. B., Gross, M., Helzlsouer, K., Jacobs, E. J., LaCroix, A., Zheng, W., and 59 others.
|
|
<strong>Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.</strong>
|
|
Nature Genet. 41: 986-990, 2009.
|
|
|
|
|
|
[PubMed: 19648918]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.429]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Aykut, B., Pushalkar, S., Chen, R., Li, Q., Abengozar, R., Kim, J. I., Shadaloey, S. A., Wu, D., Preiss, P., Verma, N., Guo, Y., Saxena, A., and 10 others.
|
|
<strong>The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL.</strong>
|
|
Nature 574: 264-267, 2019.
|
|
|
|
|
|
[PubMed: 31578522]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-019-1608-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Badgley, M. A., Kremer, D. M., Maurer, H. C., DelGiorno, K. E., Lee, H.-J., Purohit, V., Sagalovskiy, I. R., Ma, A., Kapilian, J., Firl, C. E. M., Decker, A. R., Sastra, S. A., and 18 others.
|
|
<strong>Cysteine depletion induces pancreatic tumor ferroptosis in mice.</strong>
|
|
Science 368: 85-89, 2020.
|
|
|
|
|
|
[PubMed: 32241947]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.aaw9872]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., Nourse, C., Murtaugh, L. C., and 91 others.
|
|
<strong>Genomic analyses identify molecular subtypes of pancreatic cancer.</strong>
|
|
Nature 531: 47-52, 2016.
|
|
|
|
|
|
[PubMed: 26909576]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature16965]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Banke, M. G., Mulvihill, J. J., Aston, C. E.
|
|
<strong>Inheritance of pancreatic cancer in pancreatic cancer-prone families.</strong>
|
|
Med. Clin. North Am. 84: 677-690, 2000.
|
|
|
|
|
|
[PubMed: 10872424]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0025-7125(05)70250-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Beatty, G. L., Chiorean, E. G., Fishman, M. P., Saboury, B., Teitelbaum, U. R., Sun, W., Huhn, R. D., Song, W., Li, D., Sharp, L. L., Torigian, D. A., O'Dwyer, P. J., Vonderheide, R. H.
|
|
<strong>CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans.</strong>
|
|
Science 331: 1612-1616, 2011.
|
|
|
|
|
|
[PubMed: 21436454]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1198443]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berman, D. M., Karhadkar, S. S., Maitra, A., Montes de Oca, R., Gerstenblith, M. R., Briggs, K., Parker, A. R., Shimada, Y., Eshleman, J. R., Watkins, D. N., Beachy, P. A.
|
|
<strong>Widespread requirement for hedgehog ligand stimulation in growth of digestive tract tumours.</strong>
|
|
Nature 425: 846-851, 2003.
|
|
|
|
|
|
[PubMed: 14520411]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature01972]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., Wu, J., Chang, D. K., Cowley, M. J., and 116 others.
|
|
<strong>Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.</strong>
|
|
Nature 491: 399-405, 2012.
|
|
|
|
|
|
[PubMed: 23103869]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11547]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Boring, C. C., Squires, T. S., Tong, T.
|
|
<strong>Cancer statistics, 1993.</strong>
|
|
CA Cancer J. Clin. 43: 7-26, 1993.
|
|
|
|
|
|
[PubMed: 8422609]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3322/canjclin.43.1.7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Caldas, C., Hahn, S. A., da Costa, L. T., Redston, M. S., Schutte, M., Seymour, A. B., Weinstein, C. L., Hruban, R. H., Yeo, C. J., Kern, S. E.
|
|
<strong>Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma.</strong>
|
|
Nature Genet. 8: 27-32, 1994. Note: Erratum: Nature Genet. 8: 410 only, 1994.
|
|
|
|
|
|
[PubMed: 7726912]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0994-27]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Campbell, P. J., Yachida, S., Mudie, L. J., Stephens, P. J., Pleasance, E. D., Stebbings, L. A., Morsberger, L. A., Latimer, C., McLaren, S., Lin, M.-L., McBride, D. J., Varela, I., and 13 others.
|
|
<strong>The patterns and dynamics of genomic instability in metastatic pancreatic cancer.</strong>
|
|
Nature 467: 1109-1113, 2010.
|
|
|
|
|
|
[PubMed: 20981101]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09460]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Dey, P., Baddour, J., Muller, F., Wu, C. C., Wang, H., Liao, W.-T., Lan, Z., Chen, A., Gutschner, T., Kang, Y., Fleming, J., Satani, N., and 13 others.
|
|
<strong>Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer.</strong>
|
|
Nature 542: 119-123, 2017.
|
|
|
|
|
|
[PubMed: 28099419]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature21052]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ehrenthal, D., Haeger, L., Griffin, T., Compton, C.
|
|
<strong>Familial pancreatic adenocarcinoma in three generations: a case report and a review of the literature.</strong>
|
|
Cancer 59: 1661-1664, 1987.
|
|
|
|
|
|
[PubMed: 3828965]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1097-0142(19870501)59:9<1661::aid-cncr2820590923>3.0.co;2-h]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Engle, D. D., Tiriac, H., Rivera, K. D., Pommier, A., Whalen, S., Oni, T. E., Alagesan, B., Lee, E. J., Yao, M. A., Lucito, M. S., Spielman, B., Da Silva, B., and 16 others.
|
|
<strong>The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice.</strong>
|
|
Science 364: 1156-1162, 2019.
|
|
|
|
|
|
[PubMed: 31221853]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.aaw3145]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Evans, J. P., Burke, W., Chen, R., Bennett, R. L., Schmidt, R. A., Patchen Dellinger, E., Kimmey, M., Crispin, D., Brentnall, T. A., Byrd, D. R.
|
|
<strong>Familial pancreatic adenocarcinoma: association with diabetes and early molecular diagnosis.</strong>
|
|
J. Med. Genet. 32: 330-335, 1995.
|
|
|
|
|
|
[PubMed: 7616537]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.32.5.330]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Friedman, J. M., Fialkow, P. J.
|
|
<strong>Familial carcinoma of the pancreas.</strong>
|
|
Clin. Genet. 9: 463-469, 1976.
|
|
|
|
|
|
[PubMed: 1269168]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1399-0004.1976.tb01598.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ghiorzo, P., Fornarini, G., Sciallero, S., Battistuzzi, L., Belli, F., Bernard, L., Bonelli, L., Borgonovo, G., Bruno, W., De Cian, F., DeCensi, A., Filauro, M., and 11 others.
|
|
<strong>CDKN2A is the main susceptibility gene in Italian pancreatic cancer families.</strong>
|
|
J. Med. Genet. 49: 164-170, 2012.
|
|
|
|
|
|
[PubMed: 22368299]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2011-100281]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Heaphy, C. M., de Wilde, R. F., Jiao, Y., Klein, A. P., Edil, B. H., Shi, C., Bettegowda, C., Rodriguez, F. J., Eberhart, C. G., Hebbar, S., Offerhaus, G. J., McLendon, R., and 13 others.
|
|
<strong>Altered telomeres in tumors with ATRX and DAXX mutations.</strong>
|
|
Science 333: 425 only, 2011.
|
|
|
|
|
|
[PubMed: 21719641]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1207313]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hruban, R. H., Goggins, M., Parsons, J., Kern, S. E.
|
|
<strong>Progression model for pancreatic cancer.</strong>
|
|
Clin. Cancer Res. 6: 2969-2972, 2000.
|
|
|
|
|
|
[PubMed: 10955772]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jermusyk, A., Zhong, J., Connelly, K. E., Gordon, N., Perera, S., Abdolalizadeh, E., Zhang, T., O'Brien, A., Hoskins, J. W., Collins, I., Eiser, D., Yuan, C., and 15 others.
|
|
<strong>A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and secretion and confers risk of pancreatic cancer.</strong>
|
|
Am. J. Hum. Genet. 108: 1852-1865, 2021.
|
|
|
|
|
|
[PubMed: 34559995]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2021.09.002]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jiao, Y., Shi, C., Edil, B. H., de Wilde, R. F., Klimstra, D. S., Maitra, A., Schulick, R. D., Tang, L. H., Wolfgang, C. L., Choti, M. A., Velculescu, V. E., Diaz, L. A., Jr., Vogelstein, B., Kinzler, K. W., Hruban, R. H., Papadopoulos, N.
|
|
<strong>DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors.</strong>
|
|
Science 331: 1199-1203, 2011.
|
|
|
|
|
|
[PubMed: 21252315]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1200609]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., Hong, S.-M., Fu, B., and 24 others.
|
|
<strong>Core signaling pathways in human pancreatic cancers revealed by global genomic analyses.</strong>
|
|
Science 321: 1801-1806, 2008.
|
|
|
|
|
|
[PubMed: 18772397]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1164368]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liu, C., Karam, R., Zhou, Y., Su, F., Ji, Y., Li, G., Xu, G., Lu, L., Wang, C., Song, M., Zhu, J., Wang, Y., Zhao, Y., Foo, W. C., Zuo, M., Valasek, M. A., Javle, M., Wilkinson, M. F., Lu, Y.
|
|
<strong>The UPF1 RNA surveillance gene is commonly mutated in pancreatic adenosquamous carcinoma.</strong>
|
|
Nature Med. 20: 596-598, 2014.
|
|
|
|
|
|
[PubMed: 24859531]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm.3548]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Liu, Q., Yan, Y.-X., McClure, M., Nakagawa, H., Fujimura, F., Rustgi, A. K.
|
|
<strong>MTS-1 (CDKN2) tumor suppressor gene deletions are a frequent event in esophagus squamous cancer and pancreatic adenocarcinoma cell lines.</strong>
|
|
Oncogene 10: 619-622, 1995.
|
|
|
|
|
|
[PubMed: 7845688]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lowenfels, A. B., Maisonneuve, P., DiMagno, E. P., Elitsur, Y., Gates, L. K., Jr., Perrault, J., Whitcomb, D. C., The International Hereditary Pancreatitis Study Group.
|
|
<strong>Hereditary pancreatitis and the risk of pancreatic cancer.</strong>
|
|
J. Nat. Cancer Inst. 89: 442-446, 1997.
|
|
|
|
|
|
[PubMed: 9091646]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/jnci/89.6.442]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lynch, H. T., Fusaro,L., Smyrk, T. C., Watson, P., Lanspa, S., Lynch, J. F.
|
|
<strong>Medical genetic study of eight pancreatic cancer-prone families.</strong>
|
|
Cancer Invest. 13: 141-149, 1995.
|
|
|
|
|
|
[PubMed: 7874567]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3109/07357909509011683]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
MacDermott, R. P., Kramer, P.
|
|
<strong>Adenocarcinoma of the pancreas in 4 siblings.</strong>
|
|
Gastroenterology 65: 137-139, 1973.
|
|
|
|
|
|
[PubMed: 4720820]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
McWilliams, R. R., Rabe, K. G., Olswold, C., De Andrade, M., Petersen, G. M.
|
|
<strong>Risk of malignancy in first-degree relatives of patients with pancreatic carcinoma.</strong>
|
|
Cancer 104: 388-394, 2005.
|
|
|
|
|
|
[PubMed: 15912495]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/cncr.21166]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Melo, S. A., Luecke, L. B., Kahlert, C., Fernandez, A. F., Gammon, S. T., Kaye, J., LeBleu, V. S., Mittendorf, E. A., Weitz, J., Rahbari, N., Reissfelder, C., Pilarsky, C., Fraga, M. F., Piwnica-Worms, D., Kalluri, R.
|
|
<strong>Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.</strong>
|
|
Nature 523: 177-182, 2015. Note: Erratum: Nature 610: E15-E17, 2022.
|
|
|
|
|
|
[PubMed: 26106858]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature14581]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Notta, F., Chan-Seng-Yue, M., Lemire, M., Li, Y., Wilson, G. W., Connor, A. A., Denroche, R. E., Liang, S.-B., Brown, A. M. K., Kim, J. C., Wang, T., Simpson, J. T., and 34 others.
|
|
<strong>A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns.</strong>
|
|
Nature 538: 378-382, 2016. Note: Erratum: Nature 542: 124 only, 2017.
|
|
|
|
|
|
[PubMed: 27732578]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature19823]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., Frese, K. K., DeNicola, G., and 25 others.
|
|
<strong>Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer.</strong>
|
|
Science 324: 1457-1461, 2009.
|
|
|
|
|
|
[PubMed: 19460966]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1171362]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Perera, R. M., Stoykova, S., Nicolay, B. N., Ross, K. N., Fitamant, J., Boukhali, M., Lengrand, J., Deshpande, V., Selig, M. K., Ferrone, C. R., Settleman, J., Stephanopoulos, G., Dyson, N. J., Zoncu, R., Ramaswamy, S., Haas, W., Bardeesy, N.
|
|
<strong>Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism.</strong>
|
|
Nature 524: 361-365, 2015.
|
|
|
|
|
|
[PubMed: 26168401]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature14587]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Petersen, G. M., Amundadottir, L., Fuchs, C. S., Kraft, P., Stolzenberg-Solomon, R. Z., Jacobs, K. B., Arslan, A. A., Bueno-de-Mesquita, H. B., Gallinger, S., Gross, M., Helzlsouer, K., Holly, E. A., and 61 others.
|
|
<strong>A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.</strong>
|
|
Nature Genet. 42: 224-228, 2010.
|
|
|
|
|
|
[PubMed: 20101243]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.522]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reimer, R. R., Fraumeni, J. F., Jr., Ozols, R. F., Bender, R.
|
|
<strong>Pancreatic cancer in father and son. (Letter)</strong>
|
|
Lancet 309: 911 only, 1977. Note: Originally Volume I.
|
|
|
|
|
|
[PubMed: 67325]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0140-6736(77)91244-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rosenfeldt, M. T., O'Prey, J., Morton, J. P., Nixon, C., MacKay, G., Mrowinska, A., Au, A., Rai, T. S., Zheng, L., Ridgway, R., Adams, P. D., Anderson, K. I., Gottlieb, E., Sansom, O. J., Ryan, K. M.
|
|
<strong>p53 status determines the role of autophagy in pancreatic tumour development.</strong>
|
|
Nature 504: 296-300, 2013.
|
|
|
|
|
|
[PubMed: 24305049]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature12865]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Seifert, L., Werba, G., Tiwari, S., Giao Ly, N. N., Alothman, S., Alqunaibit, D., Avanzi, A., Barilla, R., Daley, D., Greco, S. H., Torres-Hernandez, A., Pergamo, M., and 10 others.
|
|
<strong>The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.</strong>
|
|
Nature 532: 245-249, 2016. Note: Erratum: Nature 591: E28, 2021.
|
|
|
|
|
|
[PubMed: 27049944]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature17403]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shi, Y., Gao, W., Lytle, N. K., Huang, P., Yuan, X., Dann, A. M., Ridinger-Saison, M., DelGiorno, K. E., Antal, C. E., Liang, G., Atkins, A. R., Erikson, G., and 25 others.
|
|
<strong>Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.</strong>
|
|
Nature 569: 131-135, 2019. Note: Erratum: Nature 600: E18, 2021.
|
|
|
|
|
|
[PubMed: 30996350]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-019-1130-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Son, J., Lyssiotis, C. A., Ying, H., Wang, X., Hua, S., Ligorio, M., Perera, R. M., Ferrone, C. R., Mullarky, E., Shyh-Chang, N., Kang, Y., Fleming, J. B., Bardeesy, N., Asara, J. M., Haigis, M. C., DePinho, R. A., Cantley, L. C., Kimmelman, A. C.
|
|
<strong>Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway.</strong>
|
|
Nature 496: 101-105, 2013. Note: Erratum: Nature 499: 504 only, 2013.
|
|
|
|
|
|
[PubMed: 23535601]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature12040]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Swift, M., Sholman, L., Perry, M., Chase, C.
|
|
<strong>Malignant neoplasms in the families of patients with ataxia-telangiectasia.</strong>
|
|
Cancer Res. 36: 209-215, 1976.
|
|
|
|
|
|
[PubMed: 1248000]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Thayer, S. P., di Magliano, M. P., Heiser, P. W., Nielsen, C. M., Roberts, D. J., Lauwers, G. Y., Qi, Y. P., Gysin, S., Fernandez-del Castillo, C., Yajnik, V., Antoniu, B., McMahon, M., Warshaw, A. L., Hebrok, M.
|
|
<strong>Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis.</strong>
|
|
Nature 425: 851-856, 2003.
|
|
|
|
|
|
[PubMed: 14520413]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature02009]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., Quek, K., Quinn, M. C. J., Robertson, A. J., and 78 others.
|
|
<strong>Whole genomes redefine the mutational landscape of pancreatic cancer.</strong>
|
|
Nature 518: 495-501, 2015.
|
|
|
|
|
|
[PubMed: 25719666]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature14169]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Whelan, A. J., Bartsch, D., Goodfellow, P. J.
|
|
<strong>Brief report: a familial syndrome of pancreatic cancer and melanoma with a mutation in the CDKN2 tumor-suppressor gene.</strong>
|
|
New Eng. J. Med. 333: 975-977, 1995.
|
|
|
|
|
|
[PubMed: 7666917]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199510123331505]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yachida, S., Jones, S., Bozic, I., Antal, T., Leary, R., Fu, B., Kamiyama, M., Hruban, R. H., Eshleman, J. R., Nowak, M. A., Velculescu, V. E., Kinzler, K. W., Vogelstein, B., Iacobuzio-Donahue, C. A.
|
|
<strong>Distant metastasis occurs late during the genetic evolution of pancreatic cancer.</strong>
|
|
Nature 467: 1114-1117, 2010.
|
|
|
|
|
|
[PubMed: 20981102]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09515]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamamoto, K., Venida, A., Yano, J., Biancur, D. E., Kakiuchi, M., Gupta, S., Sohn, A. S. W., Mukhopadhyay, S., Lin, E. Y., Parker, S. J., Banh, R. S., Paulo, J. A., Wen, K. W., Debnath, J., Kim, G. E., Mancias, J. D., Fearon, D. T., Perera, R. M., Kimmelman, A. C.
|
|
<strong>Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I.</strong>
|
|
Nature 581: 100-105, 2020.
|
|
|
|
|
|
[PubMed: 32376951]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-020-2229-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yao, W., Rose, J. L., Wang, W., Seth, S., Jiang, H., Taguchi, A., Liu, J., Yan, L., Kapoor, A., Hou, P., Chen, Z., Wang, Q., and 26 others.
|
|
<strong>Syndecan 1 is a critical mediator of macropinocytosis in pancreatic cancer.</strong>
|
|
Nature 568: 410-414, 2019.
|
|
|
|
|
|
[PubMed: 30918400]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-019-1062-1]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zhen, D. B., Rabe, K. G., Gallinger, S., Syngal, S., Schwartz, A. G., Goggins, M. G., Hruban, R. H., Cote, M. L., McWilliams, R. R., Roberts, N. J., Cannon-Albright, L. A., Li, D., Moyes, K., Wenstrup, R. J., Hartman, A.-R., Seminara, D., Klein, A. P., Petersen, G. M.
|
|
<strong>BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study.</strong>
|
|
Genet. Med. 17: 569-577, 2015.
|
|
|
|
|
|
[PubMed: 25356972]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/gim.2014.153]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Zheng, J., Huang, X., Tan, W., Yu, D., Du, Z., Chang, J., Wei, L., Han, Y., Wang, C., Che, X., Zhou, Y., Miao, X., and 12 others.
|
|
<strong>Pancreatic cancer risk variant in LINC00673 creates a miR-1231 binding site and interferes with PTPN11 degradation.</strong>
|
|
Nature Genet. 48: 747-757, 2016.
|
|
|
|
|
|
[PubMed: 27213290]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.3568]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
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|
|
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|
|
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|
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Contributors:
|
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|
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|
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|
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|
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Bao Lige - updated : 11/15/2021<br>Ada Hamosh - updated : 09/16/2020<br>Ada Hamosh - updated : 09/08/2020<br>Ada Hamosh - updated : 03/27/2020<br>Ada Hamosh - updated : 12/18/2019<br>Ada Hamosh - updated : 09/19/2019<br>Ada Hamosh - updated : 09/12/2019<br>Ada Hamosh - updated : 08/27/2019<br>Ada Hamosh - updated : 01/19/2018<br>Ada Hamosh - updated : 09/30/2016<br>Patricia A. Hartz - updated : 08/16/2016<br>Ada Hamosh - updated : 02/03/2016<br>Ada Hamosh - updated : 10/19/2015<br>Ada Hamosh - updated : 9/24/2015<br>Ada Hamosh - updated : 9/11/2015<br>Ada Hamosh - updated : 8/29/2014<br>Ada Hamosh - updated : 1/13/2014<br>Ada Hamosh - updated : 5/30/2013<br>Ada Hamosh - updated : 12/14/2012<br>Cassandra L. Kniffin - updated : 4/10/2012<br>Ada Hamosh - updated : 9/2/2011<br>Ada Hamosh - updated : 6/6/2011<br>Ada Hamosh - updated : 4/8/2011<br>Ada Hamosh - updated : 2/15/2011<br>Ada Hamosh - updated : 6/18/2010<br>Anne M. Stumpf - reorganized : 4/9/2010<br>Ada Hamosh - updated : 11/10/2009<br>Ada Hamosh - updated : 7/9/2009<br>Ada Hamosh - updated : 6/16/2009<br>Cassandra L. Kniffin - updated : 3/30/2009<br>Ada Hamosh - updated : 10/20/2008<br>Matthew B. Gross - reorganized : 9/8/2008<br>Marla J. F. O'Neill - updated : 10/6/2005<br>Ada Hamosh - updated : 9/25/2003<br>Victor A. McKusick - updated : 9/19/2002<br>Victor A. McKusick - updated : 8/15/2002<br>Victor A. McKusick - updated : 4/12/2002<br>Victor A. McKusick - updated : 2/25/2002<br>Victor A. McKusick - updated : 11/30/1998<br>Clair A. Francomano - updated : 5/15/1995
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
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|
|
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|
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|
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|
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Victor A. McKusick : 6/4/1986
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|
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|
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carol : 01/21/2023<br>alopez : 07/15/2022<br>carol : 02/14/2022<br>mgross : 11/15/2021<br>carol : 04/23/2021<br>carol : 09/17/2020<br>alopez : 09/16/2020<br>alopez : 09/08/2020<br>alopez : 03/27/2020<br>alopez : 12/18/2019<br>alopez : 11/26/2019<br>alopez : 09/19/2019<br>alopez : 09/12/2019<br>alopez : 08/27/2019<br>alopez : 01/19/2018<br>alopez : 09/30/2016<br>mgross : 08/16/2016<br>alopez : 02/03/2016<br>alopez : 10/19/2015<br>alopez : 9/24/2015<br>alopez : 9/11/2015<br>alopez : 8/29/2014<br>alopez : 1/13/2014<br>alopez : 10/1/2013<br>alopez : 5/30/2013<br>alopez : 12/18/2012<br>alopez : 12/17/2012<br>terry : 12/14/2012<br>terry : 9/17/2012<br>alopez : 4/10/2012<br>alopez : 3/8/2012<br>alopez : 3/7/2012<br>mgross : 10/31/2011<br>alopez : 9/2/2011<br>terry : 9/2/2011<br>alopez : 6/14/2011<br>terry : 6/6/2011<br>alopez : 4/11/2011<br>terry : 4/8/2011<br>alopez : 2/18/2011<br>terry : 2/15/2011<br>alopez : 9/23/2010<br>terry : 9/21/2010<br>alopez : 6/29/2010<br>terry : 6/18/2010<br>terry : 6/18/2010<br>alopez : 5/25/2010<br>alopez : 4/27/2010<br>alopez : 4/15/2010<br>alopez : 4/9/2010<br>alopez : 4/8/2010<br>alopez : 11/12/2009<br>terry : 11/10/2009<br>alopez : 7/16/2009<br>terry : 7/9/2009<br>alopez : 6/23/2009<br>terry : 6/16/2009<br>wwang : 4/10/2009<br>ckniffin : 3/30/2009<br>terry : 3/13/2009<br>alopez : 10/22/2008<br>terry : 10/20/2008<br>mgross : 9/8/2008<br>wwang : 10/12/2005<br>terry : 10/6/2005<br>mgross : 4/13/2005<br>alopez : 10/31/2003<br>tkritzer : 10/1/2003<br>terry : 9/25/2003<br>terry : 2/26/2003<br>terry : 12/17/2002<br>tkritzer : 9/25/2002<br>tkritzer : 9/24/2002<br>carol : 9/19/2002<br>carol : 9/19/2002<br>tkritzer : 8/21/2002<br>tkritzer : 8/19/2002<br>terry : 8/15/2002<br>alopez : 4/16/2002<br>terry : 4/12/2002<br>mgross : 2/26/2002<br>terry : 2/25/2002<br>carol : 4/3/2001<br>carol : 6/12/1999<br>carol : 5/24/1999<br>carol : 11/30/1998<br>mark : 4/9/1996<br>mark : 12/8/1995<br>terry : 12/8/1995<br>terry : 7/28/1995<br>mark : 7/24/1995<br>davew : 6/6/1994<br>mimadm : 3/11/1994<br>supermim : 3/17/1992
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