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Entry
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- #137215 - DIFFUSE GASTRIC AND LOBULAR BREAST CANCER SYNDROME; DGLBC
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- OMIM
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<p>
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<span class="h4">#137215</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/137215"><strong>Clinical Synopsis</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="#diagnosis">Diagnosis</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="#pathogenesis">Pathogenesis</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="#nomenclature">Nomenclature</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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<div><a href="https://clinicaltrials.gov/search?cond=DIFFUSE GASTRIC AND LOBULAR BREAST CANCER SYNDROME" 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=8758&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.ncbi.nlm.nih.gov/books/NBK1139/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/8514" 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/condition/hereditary-diffuse-gastric-cancer" 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=137215[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=26106" 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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<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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</a>
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</span>
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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:0080764" 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/137215" 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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<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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<a id="number" class="mim-anchor"></a>
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 26106<br />
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<strong>DO:</strong> 0080764<br />
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">ICD+</a>
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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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137215
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</span>
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</span>
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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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DIFFUSE GASTRIC AND LOBULAR BREAST CANCER SYNDROME; DGLBC
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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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GASTRIC CANCER, HEREDITARY DIFFUSE; HDGC<br />
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GASTRIC CANCER, FAMILIAL DIFFUSE BREAST CANCER, LOBULAR; LBC
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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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<a id="includedTitles" class="mim-anchor"></a>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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DIFFUSE GASTRIC AND LOBULAR BREAST CANCER SYNDROME WITH CLEFT LIP AND WITH OR WITHOUT CLEFT PALATE, INCLUDED
|
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</span>
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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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<tr class="active">
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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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<tbody>
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<td>
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<span class="mim-font">
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<a href="/geneMap/16/582?start=-3&limit=10&highlight=582">
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16q22.1
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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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Diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate
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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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<a href="/entry/137215"> 137215 </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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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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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<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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CDH1
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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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<a href="/entry/192090"> 192090 </a>
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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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<div class="btn-group ">
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<a href="/clinicalSynopsis/137215" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<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')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/137215" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/137215" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<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>
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<p />
|
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
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<div class="small" style="margin: 5px">
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<strong> INHERITANCE </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
|
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<span class="mim-font">
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|
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- 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 />
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</span>
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</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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<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<em> Mouth </em>
|
|
</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cleft lip (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80281008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80281008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q36" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q36</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q36.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q36.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/749.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/749.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008924</a>, <a href="https://bioportal.bioontology.org/search?q=C4321245&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4321245</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000204" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000204</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0410030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410030</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0410030" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410030</a>]</span><br /> -
|
|
Cleft palate (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63567004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63567004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/87979003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">87979003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q35.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q35.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/749.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/749.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">749.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837218&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837218</a>, <a href="https://bioportal.bioontology.org/search?q=C2981150&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2981150</a>, <a href="https://bioportal.bioontology.org/search?q=C2240378&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2240378</a>, <a href="https://bioportal.bioontology.org/search?q=C0008925&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008925</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000175" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000175</a>]</span><br />
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|
|
</span>
|
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</div>
|
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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> NEOPLASIA </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Gastric cancer, diffuse type, poorly differentiated, high-grade submucosal lesions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3549741&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3549741</a>]</span><br /> -
|
|
Signet ring cell adenocarcinoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/87737001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">87737001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0206696&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0206696</a>]</span><br /> -
|
|
Breast cancer, lobular <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3549742&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3549742</a>]</span><br /> -
|
|
Colorectal cancer (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1286877004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1286877004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5848476&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5848476</a>, <a href="https://bioportal.bioontology.org/search?q=C0009402&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009402</a>]</span><br />
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|
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</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">
|
|
|
|
- Average age at onset 38 years<br /> -
|
|
Onset in teens has been reported<br /> -
|
|
Penetrance of 70 to 80% over a lifetime in heterozygous mutation carriers<br /> -
|
|
Up to 60% of female mutation carriers develop lobular breast cancer<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
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</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">
|
|
|
|
- Caused by mutation in the cadherin-1 gene (CDH1, <a href="/entry/192090#0002">192090.0002</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
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|
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</div>
|
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|
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</div>
|
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|
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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 />
|
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</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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|
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div id="mimTextFold" class="collapse in ">
|
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<span class="mim-text-font">
|
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<p>A number sign (#) is used with this entry because of evidence that diffuse gastric and lobular breast cancer syndrome (DGLBC) is caused by heterozygous germline mutation in the E-cadherin gene (CDH1; <a href="/entry/192090">192090</a>) on chromosome 16q22.</p><p>Somatic mutation in the CDH1 gene has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer.</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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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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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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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Diffuse gastric cancer and lobular breast cancer syndrome (DGLBC) is an autosomal dominant cancer predisposition syndrome. Heterozygous CDH1 mutation carriers have a 70 to 80% lifetime risk of developing diffuse gastric cancer. In addition to gastric cancer, up to 60% of female mutation carriers develop lobular carcinoma of the breast, and some carriers may develop colorectal cancer. Identification of mutation carriers is important, because the characteristic microscopic foci of signet ring cell adenocarcinoma in HDGC usually involves the submucosa and is often not readily detectable by routine upper endoscopy screening (summary by <a href="#7" class="mim-tip-reference" title="Fitzgerald, R. C., Hardwick, R., Huntsman, D., Carneiro, F., Guilford, P., Blair, V., Chung, D. C., Norton, J., Ragunath, K., Van Grieken, N. C., Dwerryhouse, S., Caldas, C., International Gastric Cancer Linkage Consortium. <strong>Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research.</strong> J. Med. Genet. 47: 436-444, 2010. Note: Erratum: J. Med. Genet. 48: 216 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20591882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20591882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20591882[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/10.1136/jmg.2009.074237" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20591882">Fitzgerald et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20591882" 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>DGLBC is considered to be a distinct disease entity from the more common sporadic occurrence of gastric cancer (<a href="/entry/613659">613659</a>), which can be associated with environmental factors such as Helicobacter pylori infection, high-fat diet, or smoking and is often associated with somatic mutations in disease tissue.</p>
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<p><a href="#14" class="mim-tip-reference" title="Jones, E. G. <strong>Familial gastric cancer.</strong> New Zealand Med. J. 63: 287-296, 1964.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14158754/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14158754</a>]" pmid="14158754">Jones (1964)</a> described 3 multigenerational Maori families from New Zealand segregating early-onset familial gastric cancer. These families were later studied in detail by <a href="#11" class="mim-tip-reference" title="Guilford, P., Hopkins, J., Harraway, J., McLeod, M., McLeod, N., Harawira, P., Taite, H., Scoular, R., Miller, A., Reeve, A. E. <strong>E-cadherin germline mutations in familial gastric cancer.</strong> Nature 392: 402-405, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537325</a>] [<a href="https://doi.org/10.1038/32918" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537325">Guilford et al. (1998)</a>. In 1 family, 25 members ranging in age from 14 years upwards had died over 30 years. The majority of cases occurred before age 40 years, which was in marked contrast to the general experience in New Zealand, where about 80% of gastric cancers occur in people older than 60 years. There was no evidence of an increased cancer rate of other organs in this family. Pathology showed histologically poorly differentiated, high-grade, diffuse gastric cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9537325+14158754" 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="#15" class="mim-tip-reference" title="Kakiuchi, H., Itoh, F., Kusano, M., Adachi, Y., Mita, H., Mihara, M., Matsuno, K., Endo, T., Hinoda, Y., Hosokawa, M., Imai, K. <strong>Familial gastric cancer in the Japanese population is frequently located at the cardiac region.</strong> Tumour Biol. 20: 235-241, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10436415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10436415</a>] [<a href="https://doi.org/10.1159/000030069" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10436415">Kakiuchi et al. (1999)</a> studied the clinical features of the probands of 16 Japanese gastric cancer families, which was defined as the existence of 3 or more family members with gastric cancer in at least 2 successive generations. These patients developed cancers more frequently in the cardiac region of the stomach. In addition, the cancers were more often of the undifferentiated type, and were more frequently associated with disseminated peritoneal and liver metastases compared to sporadic cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10436415" 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="#20" class="mim-tip-reference" title="Richards, F. M., McKee, S. A., Rajpar, M. H., Cole, T. R. P., Evans, D. G. R., Jankowski, J. A., McKeown, C., Sanders, D. S. A., Maher, E. R. <strong>Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer.</strong> Hum. Molec. Genet. 8: 607-610, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10072428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10072428</a>] [<a href="https://doi.org/10.1093/hmg/8.4.607" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10072428">Richards et al. (1999)</a> reported a family from the U.K. in which 6 individuals developed diffuse gastric cancer. In addition to the 6 members with gastric cancer, 1 member of the family developed adenocarcinoma of the rectum at the age of 30 years. Genetic analysis identified a heterozygous mutation in the CDH1 gene (<a href="/entry/192090#0008">192090.0008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10072428" 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="Huntsman, D. G., Carneiro, F., Lewis, F. R., MacLeod, P. M., Hayashi, A., Monaghan, K. G., Maung, R., Seruca, R., Jackson, C. E., Caldas, C. <strong>Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations.</strong> New Eng. J. Med. 344: 1904-1909, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11419427/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11419427</a>] [<a href="https://doi.org/10.1056/NEJM200106213442504" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11419427">Huntsman et al. (2001)</a> described genetic screening, surgical management, and pathologic findings in young persons with truncating CDH1 mutations (<a href="/entry/192090#0012">192090.0012</a>; <a href="/entry/192090#0013">192090.0013</a>) in 2 unrelated families with hereditary diffuse gastric cancer reported by <a href="#9" class="mim-tip-reference" title="Gayther, S. A., Gorringe, K. L., Ramus, S. J., Huntsman, D., Roviello, F., Grehan, N., Machado, J. C., Pinto, E., Seruca, R., Halling, K., MacLeod, P., Powell, S. M., Jackson, C. E., Ponder, B. A. J., Caldas, C. <strong>Identification of germ-line E-cadherin mutations in gastric cancer families of European origin.</strong> Cancer Res. 58: 4086-4089, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9751616/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9751616</a>]" pmid="9751616">Gayther et al. (1998)</a>. Total gastrectomy was performed prophylactically in 5 carriers of mutations who were between 22 and 40 years of age. In each case, superficial infiltrates of malignant signet ring cells were identified in surgical samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11419427+9751616" 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="#5" class="mim-tip-reference" title="Chun, Y. S., Lindor, N. M., Smyrk, T. C., Petersen, B. T., Burgart, L. J., Guilford, P. J., Donohue, J. H. <strong>Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated?</strong> Cancer 92: 181-187, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11443625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11443625</a>] [<a href="https://doi.org/10.1002/1097-0142(20010701)92:1<181::aid-cncr1307>3.0.co;2-j" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11443625">Chun et al. (2001)</a> reported a family with a strong history of HDGC. Five family members, including a sister and brother and 3 first cousins, underwent endoscopic evaluations, which were negative for malignancy, and elected to undergo a prophylactic total gastrectomy with Roux-en-Y esophagojejunostomy. Intramucosal signet ring cell adenocarcinoma was found in various regions of the stomach in all 5 patients, and all 5 demonstrated diminished or absent E-cadherin reactivity in the cancerous mucosa. The age of the 5 patients at the time of surgery varied from 40 to 63 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11443625" 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="#2" class="mim-tip-reference" title="Brooks-Wilson, A. R., Kaurah, P., Suriano, G., Leach, S., Senz, J., Grehan, N., Butterfield, Y. S. N., Jeyes, J., Schinas, J., Bacani, J., Kelsey, M., Ferreira, P., and 19 others. <strong>Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria.</strong> J. Med. Genet. 41: 508-517, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15235021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15235021</a>] [<a href="https://doi.org/10.1136/jmg.2004.018275" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15235021">Brooks-Wilson et al. (2004)</a> reported 10 different families with hereditary gastric cancer who had germline mutations in the CDH1 gene. There were multiple cases of breast cancers, including pathologically confirmed lobular breast cancer, in these families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15235021" 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 retrospective study of French patients who underwent genetic testing for germline mutations in the CDH1 gene, <a href="#1" class="mim-tip-reference" title="Benusiglio, P. R., Malka, D., Rouleau, E., De Pauw, A., Buecher, B., Nogues, C., Fourme, E., Colas, C., Coulet, F., Warcoin, M., Grandjouan, S., Sezeur, A., Laurent-Puig, P., Moliere, D., Tlemsani, C., Di Maria, M., Byrde, V., Delaloge, S., Blayau, M., Caron, O. <strong>CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: a multicentre study.</strong> J. Med. Genet. 50: 486-489, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23709761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23709761</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-101472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23709761">Benusiglio et al. (2013)</a> found that 18 (11%) of 165 index cases carried pathogenic mutations. Eleven of these patients had a personal or family history that fulfilled diagnostic criteria delineated by <a href="#7" class="mim-tip-reference" title="Fitzgerald, R. C., Hardwick, R., Huntsman, D., Carneiro, F., Guilford, P., Blair, V., Chung, D. C., Norton, J., Ragunath, K., Van Grieken, N. C., Dwerryhouse, S., Caldas, C., International Gastric Cancer Linkage Consortium. <strong>Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research.</strong> J. Med. Genet. 47: 436-444, 2010. Note: Erratum: J. Med. Genet. 48: 216 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20591882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20591882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20591882[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/10.1136/jmg.2009.074237" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20591882">Fitzgerald et al. (2010)</a> (see DIAGNOSIS). However, 7 remaining cases did not meet the HDGC criteria: 3 women had sporadic bilateral lobular breast cancer before age 50; 3 came from families with 2 cases of DGC after age 50; and 1 had sporadic diffuse gastric cancer after age 40. Of the 3 woman with LBC before age 50, 2 were only tested for CDH1 after subsequently developing symptomatic DGC and thus meeting the criteria. The remaining woman had CDH1 testing and prophylactic gastrectomy that revealed DGC despite a negative screening endoscopy. These findings suggested that early-onset LBC might be the first manifestation of HDGC, and that a personal or family history of multiple LBCs at a young age, even in the absence of DGC, should prompt cancer geneticists to test for CDH1 germline mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23709761+20591882" 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>Diffuse Gastric and Lobular Breast Cancer Syndrome with or without Cleft Palate</em></strong></p><p>
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<a href="#8" class="mim-tip-reference" title="Frebourg, T., Oliveira, C., Hochain, P., Karam, R., Manouvrier, S., Graziadio, C., Vekemans, M., Hartmann, A., Baert-Desurmont, S., Alexandre, C., Lejeune Dumoulin, S., Marroni, C., and 16 others. <strong>Cleft lip/palate and CDH1/E-cadherin mutation in families with hereditary diffuse gastric cancer.</strong> J. Med. Genet. 43: 138-142, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15831593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15831593</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15831593[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/10.1136/jmg.2005.031385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15831593">Frebourg et al. (2006)</a> reported 2 unrelated families segregating diffuse gastric cancer and cleft palate. Genetic analysis confirmed that affected individuals with gastric cancer with or without cleft palate had heterozygous mutations in the CDH1 gene (<a href="/entry/192090#0019">192090.0019</a> and <a href="/entry/192090#0020">192090.0020</a>, respectively). In 1 family, 4 mutation carriers had diffuse gastric cancer and cleft lip/palate and 2 mutation carriers had gastric cancer without clefting. In the second family, a man and his 2 daughters had gastric cancer, a daughter with the mutation had cleft lip but no gastric cancer at age 25, and a 16-year-old son with the mutation had congenital aplasia cutis of the scalp and partial acrania (<a href="/entry/107600">107600</a>) but no known gastric cancer. Both mutations were splicing mutations generating aberrant transcripts with an in-frame deletion, removing the extracellular cadherin repeat domains involved in cell-cell adhesion. Such transcripts might encode mutant proteins with trans-dominant-negative effects. Expression of CDH1 in human embryos during critical stages of lip and palate development suggested that alteration of the E-cadherin pathway may contribute to human clefting. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15831593" 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="#3" class="mim-tip-reference" title="Caldas, C., Carneiro, F., Lynch, H. T., Yokota, J., Wiesner, G. L., Powell, S. M., Lewis, F. R., Huntsman, D. G., Pharoah, P. D. P., Jankowski, J. A., MacLeod, P., Vogelsang, H., and 12 others. <strong>Familial gastric cancer: overview and guidelines for management.</strong> J. Med. Genet. 36: 873-880, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10593993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10593993</a>]" pmid="10593993">Caldas et al. (1999)</a> reported the proceedings of the First Workshop of the International Gastric Cancer Linkage Consortium convened to produce consensus statements and guidelines for familial gastric cancer. <a href="#3" class="mim-tip-reference" title="Caldas, C., Carneiro, F., Lynch, H. T., Yokota, J., Wiesner, G. L., Powell, S. M., Lewis, F. R., Huntsman, D. G., Pharoah, P. D. P., Jankowski, J. A., MacLeod, P., Vogelsang, H., and 12 others. <strong>Familial gastric cancer: overview and guidelines for management.</strong> J. Med. Genet. 36: 873-880, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10593993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10593993</a>]" pmid="10593993">Caldas et al. (1999)</a> noted that review of pathologic samples from 8 families with inactivating germline mutations in the E-cadherin gene showed that all of the gastric cancers in these families were of diffuse type, and 2 of these had a glandular/intestinal component. Hereditary diffuse gastric cancer was defined as existing in any family in which there were (1) 2 or more documented cases of diffuse gastric cancer in first- or second-degree relatives with at least one cancer diagnosed before the age of 50; or (2) 3 or more cases of diffuse gastric cancer in first- or second-degree relatives independent of age of onset. <a href="#3" class="mim-tip-reference" title="Caldas, C., Carneiro, F., Lynch, H. T., Yokota, J., Wiesner, G. L., Powell, S. M., Lewis, F. R., Huntsman, D. G., Pharoah, P. D. P., Jankowski, J. A., MacLeod, P., Vogelsang, H., and 12 others. <strong>Familial gastric cancer: overview and guidelines for management.</strong> J. Med. Genet. 36: 873-880, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10593993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10593993</a>]" pmid="10593993">Caldas et al. (1999)</a> also noted that since 5 individuals below the age of 18 had developed diffuse gastric carcinoma, testing of minors might be justified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10593993" 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="#7" class="mim-tip-reference" title="Fitzgerald, R. C., Hardwick, R., Huntsman, D., Carneiro, F., Guilford, P., Blair, V., Chung, D. C., Norton, J., Ragunath, K., Van Grieken, N. C., Dwerryhouse, S., Caldas, C., International Gastric Cancer Linkage Consortium. <strong>Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research.</strong> J. Med. Genet. 47: 436-444, 2010. Note: Erratum: J. Med. Genet. 48: 216 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20591882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20591882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20591882[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/10.1136/jmg.2009.074237" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20591882">Fitzgerald et al. (2010)</a> presented updated consensus guidelines for HDGC, which included broadening of CDH1 testing criteria: histologic confirmation of diffuse gastric criteria is only required for 1 family member; inclusion of individuals with diffuse gastric cancer before the age of 40 years without a family history; and inclusion of individuals and families with diagnoses of both diffuse gastric cancer (including one before the age of 50 years) and lobular breast cancer. Large genomic rearrangements of CDH1 should be sought in addition to direct sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20591882" 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="#1" class="mim-tip-reference" title="Benusiglio, P. R., Malka, D., Rouleau, E., De Pauw, A., Buecher, B., Nogues, C., Fourme, E., Colas, C., Coulet, F., Warcoin, M., Grandjouan, S., Sezeur, A., Laurent-Puig, P., Moliere, D., Tlemsani, C., Di Maria, M., Byrde, V., Delaloge, S., Blayau, M., Caron, O. <strong>CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: a multicentre study.</strong> J. Med. Genet. 50: 486-489, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23709761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23709761</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-101472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23709761">Benusiglio et al. (2013)</a> suggested that the criteria for CDH1 testing put forth by <a href="#7" class="mim-tip-reference" title="Fitzgerald, R. C., Hardwick, R., Huntsman, D., Carneiro, F., Guilford, P., Blair, V., Chung, D. C., Norton, J., Ragunath, K., Van Grieken, N. C., Dwerryhouse, S., Caldas, C., International Gastric Cancer Linkage Consortium. <strong>Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research.</strong> J. Med. Genet. 47: 436-444, 2010. Note: Erratum: J. Med. Genet. 48: 216 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20591882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20591882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20591882[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/10.1136/jmg.2009.074237" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20591882">Fitzgerald et al. (2010)</a> may be too strict, and proposed that a personal or family history of 2 histologically proven lobular breast cancers before age 50, after exclusion of a germline mutation in BRCA1 and BRCA2, should be added to the criteria for CDH1 testing. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23709761+20591882" 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="#21" class="mim-tip-reference" title="van der Post, R. S., Vogelaar, I. P., Carneiro, F., Guilford, P., Huntsman, D., Hoogerbrugge, N., Caldas, C., Chelcun Schreiber, K. E., Hardwick, R. H., Ausems, M. G. E. M., Bardram, L., Benusiglio, P. R., and 36 others. <strong>Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers.</strong> J. Med. Genet. 52: 361-374, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25979631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25979631</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25979631[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/10.1136/jmedgenet-2015-103094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25979631">Van der Post et al. (2015)</a> reported the results of a multidisciplinary workshop that discussed genetic testing and management of patients with hereditary diffuse gastric cancer (DGC). The workshop recommended that CDH1 testing criteria should take into account first and second-degree relatives: (1) families with 2 or more patients with gastric cancer at any age, 1 confirmed diffuse gastric cancer; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and lobular breast cancer (LBC), 1 diagnosis before the age of 50. Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25979631" 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="Fitzgerald, R. C., Hardwick, R., Huntsman, D., Carneiro, F., Guilford, P., Blair, V., Chung, D. C., Norton, J., Ragunath, K., Van Grieken, N. C., Dwerryhouse, S., Caldas, C., International Gastric Cancer Linkage Consortium. <strong>Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research.</strong> J. Med. Genet. 47: 436-444, 2010. Note: Erratum: J. Med. Genet. 48: 216 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20591882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20591882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20591882[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/10.1136/jmg.2009.074237" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20591882">Fitzgerald et al. (2010)</a> presented updated consensus guidelines for the genetic counseling, management, and surveillance of HDGC. They recommended strong consideration of prophylactic total gastrectomy in mutation-positive individuals or, at the least, detailed endoscopic surveillance with multiple biopsies. Annual mammography and breast MRI from the age of 35 years was recommended for women. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20591882" 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="Lynch, H. T., Grady, W., Lynch, J. F., Tsuchiya, K. D., Wiesner, G., Markowitz, S. D. <strong>E-cadherin mutation-based genetic counseling and hereditary diffuse gastric carcinoma.</strong> Cancer Genet. Cytogenet. 122: 1-6, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11104024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11104024</a>] [<a href="https://doi.org/10.1016/s0165-4608(00)00273-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11104024">Lynch et al. (2000)</a> described E-cadherin mutation-based genetic counseling in an affected kindred reported by <a href="#12" class="mim-tip-reference" title="Guilford, P. J., Hopkins, J. B. W., Grady, W. M., Markowitz, S. D., Willis, J., Lynch, H., Rajput, A., Wiesner, G. L., Lindor, N. M., Burgart, L. J., Toro, T. T., Lee, D., Limacher, J.-M., Shaw, D. W., Findlay, M. P. N., Reeve, A. E. <strong>E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.</strong> Hum. Mutat. 14: 249-255, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10477433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10477433</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:3<249::AID-HUMU8>3.0.CO;2-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10477433">Guilford et al. (1999)</a>. Of 24 family members tested for the familial mutation (<a href="/entry/192090#0011">192090.0011</a>), 9 were found to be positive and 15 negative. None of the 19 patients counseled wanted results sent to their physicians once they recognized the potential for insurance discrimination. None had undergone endoscopic ultrasound. Three who were positive for the mutation expressed strong interest in prophylactic gastrectomy. Three of the 9 who tested positive were affected and had died by the time of report. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10477433+11104024" 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="#21" class="mim-tip-reference" title="van der Post, R. S., Vogelaar, I. P., Carneiro, F., Guilford, P., Huntsman, D., Hoogerbrugge, N., Caldas, C., Chelcun Schreiber, K. E., Hardwick, R. H., Ausems, M. G. E. M., Bardram, L., Benusiglio, P. R., and 36 others. <strong>Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers.</strong> J. Med. Genet. 52: 361-374, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25979631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25979631</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25979631[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/10.1136/jmedgenet-2015-103094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25979631">Van der Post et al. (2015)</a> reported the results of a multidisciplinary workshop that discussed management of patients who test positive for CDH1 pathogenic variants related to diffuse gastric cancer. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a center of expertise was advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation was recommended. Standardized endoscopic surveillance in experienced centers was recommended for those opting not to have gastrectomy, those with CDH1 variants of uncertain significance, and those that fulfill hereditary DGC criteria without germline CDH1 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25979631" 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>Diffuse gastric cancer and lobular breast cancer syndrome is an autosomal dominant cancer predisposition syndrome. <a href="#7" class="mim-tip-reference" title="Fitzgerald, R. C., Hardwick, R., Huntsman, D., Carneiro, F., Guilford, P., Blair, V., Chung, D. C., Norton, J., Ragunath, K., Van Grieken, N. C., Dwerryhouse, S., Caldas, C., International Gastric Cancer Linkage Consortium. <strong>Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research.</strong> J. Med. Genet. 47: 436-444, 2010. Note: Erratum: J. Med. Genet. 48: 216 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20591882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20591882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20591882[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/10.1136/jmg.2009.074237" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20591882">Fitzgerald et al. (2010)</a> reported that heterozygous CDH1 mutation carriers have a 70 to 80% lifetime risk of developing gastric cancer. In addition to gastric cancer, up to 60% of female mutation carriers will develop lobular carcinoma of the breast, and some carriers may develop colorectal cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20591882" 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="#16" class="mim-tip-reference" title="Lauren, P. <strong>The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification.</strong> Acta Path. Microbiol. Scand. 64: 31-49, 1965.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14320675/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14320675</a>] [<a href="https://doi.org/10.1111/apm.1965.64.1.31" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14320675">Lauren (1965)</a> defined 2 main histologic types of gastric carcinomas, a 'diffuse' type and a so-called 'intestinal' type. Diffuse tumors, as observed in HDGC, are poorly differentiated infiltrating lesions resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. This classification system was updated (<a href="#4" class="mim-tip-reference" title="Carneiro, F., Seixas, M., Sobrinho-Simoes, M. <strong>New elements for an updated classification of the carcinomas of the stomach.</strong> Path. Res. Pract. 191: 571-584, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7479380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7479380</a>] [<a href="https://doi.org/10.1016/S0344-0338(11)80878-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7479380">Carneiro et al., 1995</a>) to include 4 main types of gastric cancer: isolated cell and mixed types (representing the diffuse component); and glandular/intestinal and solid (representing the non-diffuse component). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7479380+14320675" 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 review of HDGC from a consensus statement, <a href="#7" class="mim-tip-reference" title="Fitzgerald, R. C., Hardwick, R., Huntsman, D., Carneiro, F., Guilford, P., Blair, V., Chung, D. C., Norton, J., Ragunath, K., Van Grieken, N. C., Dwerryhouse, S., Caldas, C., International Gastric Cancer Linkage Consortium. <strong>Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research.</strong> J. Med. Genet. 47: 436-444, 2010. Note: Erratum: J. Med. Genet. 48: 216 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20591882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20591882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20591882[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/10.1136/jmg.2009.074237" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20591882">Fitzgerald et al. (2010)</a> noted that histologic study of prophylactic gastrectomies almost universally showed pre-invasive lesions, including in situ signet ring carcinoma with pagetoid spread of signet ring cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20591882" 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>By linkage analysis of a large New Zealand family with autosomal dominant inheritance of diffuse gastric cancer, <a href="#11" class="mim-tip-reference" title="Guilford, P., Hopkins, J., Harraway, J., McLeod, M., McLeod, N., Harawira, P., Taite, H., Scoular, R., Miller, A., Reeve, A. E. <strong>E-cadherin germline mutations in familial gastric cancer.</strong> Nature 392: 402-405, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537325</a>] [<a href="https://doi.org/10.1038/32918" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537325">Guilford et al. (1998)</a> found significant linkage to chromosome 16q22.1 (maximum 2-point lod score of 5.04 at marker D16S752). Segregation of the disease haplotype indicated a penetrance of 70% by age 60 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537325" 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>In affected members of 3 New Zealand families with HDGC, <a href="#11" class="mim-tip-reference" title="Guilford, P., Hopkins, J., Harraway, J., McLeod, M., McLeod, N., Harawira, P., Taite, H., Scoular, R., Miller, A., Reeve, A. E. <strong>E-cadherin germline mutations in familial gastric cancer.</strong> Nature 392: 402-405, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9537325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9537325</a>] [<a href="https://doi.org/10.1038/32918" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9537325">Guilford et al. (1998)</a> identified heterozygous germline mutations in the CDH1 gene (<a href="/entry/192090#0005">192090.0005</a>-<a href="/entry/192090#0007">192090.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9537325" 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="#10" class="mim-tip-reference" title="Grady, W. M., Willis, J., Guilford, P. J., Dunbier, A. K., Toro, T. T., Lynch, H., Wiesner, G., Ferguson, K., Eng, C., Park, J.-G., Kim, S.-J., Markowitz, S. <strong>Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer.</strong> Nature Genet. 26: 16-17, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973239</a>] [<a href="https://doi.org/10.1038/79120" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973239">Grady et al. (2000)</a> noted that patients with heterozygous germline mutations in the CDH1 gene develop gastric cancer, but their cancers consistently demonstrate no loss of heterozygosity (LOH) at the CDH1 locus. They hypothesized that methylation of the CDH1 promoter might represent the 'second genetic hit' in the genesis of these tumors. The CDH1 promoter was found to be consistently unmethylated in normal stomach mucosa, whereas 3 of 6 HDGC tumors with negative CDH1 staining had aberrant CDH1 promoter methylation. Two tumors that had retained unmethylated CDH1 promoters harbored somatic CDH1 mutations. No somatic mutations were found in 2 HDGC tumors showing CDH1 promoter methylation, but sequence polymorphisms confirmed that they retained a second wildtype allele. These findings indicated that the formation of HDGC tumors requires biallelic CDH1 inactivation, which in one-half of cases is accomplished by promoter methylation of a retained wildtype allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973239" 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 with a strong history of diffuse gastric carcinoma, <a href="#5" class="mim-tip-reference" title="Chun, Y. S., Lindor, N. M., Smyrk, T. C., Petersen, B. T., Burgart, L. J., Guilford, P. J., Donohue, J. H. <strong>Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated?</strong> Cancer 92: 181-187, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11443625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11443625</a>] [<a href="https://doi.org/10.1002/1097-0142(20010701)92:1<181::aid-cncr1307>3.0.co;2-j" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11443625">Chun et al. (2001)</a> found a 1558insC germline mutation in the CDH1 gene (<a href="/entry/192090#0014">192090.0014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11443625" 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="#18" class="mim-tip-reference" title="Oliveira, C., Bordin, M. C., Grehan, N., Huntsman, D., Suriano, G., Machado, J. C., Kiviluoto, T., Aaltonen, L., Jackson, C. E., Seruca, R., Caldas, C. <strong>Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred.</strong> Hum. Mutat. 19: 510-517, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11968083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11968083</a>] [<a href="https://doi.org/10.1002/humu.10068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11968083">Oliveira et al. (2002)</a> performed germline CDH1 mutation screening in 39 kindreds with familial aggregation of gastric cancer, a subset of which fulfilled the criteria defined by the International Gastric Cancer Linkage Consortium (IGCLC) for hereditary diffuse gastric cancer. CDH1 germline mutations were detected in 4 of 11 (36.4%) HDGC families. No mutations were identified in 63.6% of HDGC families or in kindreds with familial aggregation of gastric cancer not fulfilling criteria for HDGC. These results added support to the evidence that only HDGC families harbor germline mutations in CDH1 and that genes other than CDH1 remained to be identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11968083" 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>Among 43 apparent cases of hereditary gastric cancer, <a href="#2" class="mim-tip-reference" title="Brooks-Wilson, A. R., Kaurah, P., Suriano, G., Leach, S., Senz, J., Grehan, N., Butterfield, Y. S. N., Jeyes, J., Schinas, J., Bacani, J., Kelsey, M., Ferreira, P., and 19 others. <strong>Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria.</strong> J. Med. Genet. 41: 508-517, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15235021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15235021</a>] [<a href="https://doi.org/10.1136/jmg.2004.018275" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15235021">Brooks-Wilson et al. (2004)</a> identified heterozygous mutations in the CDH1 gene in 10 different families. There were 10 loss-of-function mutations, including 2 insertions, 5 deletions, 2 splice site substitutions, and 1 complex deletion/insertion involving a splice site. They also found 3 heterozygous missense mutations that were predicted to affect conserved residues and to have deleterious effects on protein function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15235021" 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="#19" class="mim-tip-reference" title="Oliveira, C., Senz, J., Kaurah, P., Pinheiro, H., Sanges, R., Haegert, A., Corso, G., Schouten, J., Fitzgerald, R., Vogelsang, H., Keller, G., Dwerryhouse, S., and 9 others. <strong>Germline CDH1 deletions in hereditary diffuse gastric cancer families.</strong> Hum. Molec. Genet. 18: 1545-1555, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19168852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19168852</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19168852[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/10.1093/hmg/ddp046" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19168852">Oliveira et al. (2009)</a> reported 6 (6.5%) of 93 previously described mutation-negative hereditary diffuse gastric cancer probands who carried genomic deletions of the CDH1 gene (see, e.g., <a href="/entry/192090#0022">192090.0022</a> and <a href="/entry/192090#0023">192090.0023</a>). The statistically significant overrepresentation of Alu repeats around breakpoints indicated nonhomologous allelic recombination of Alu repeats as a likely mechanism for these deletions. When all mutations and deletions were considered, the overall frequency of CDH1 alterations in HDGC was approximately 46% (73 of 160), and large CDH1 deletions occurred in 3.8% of HDGC families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19168852" 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>Among 18 index patients with germline CDH1 mutations identified retrospectively, <a href="#1" class="mim-tip-reference" title="Benusiglio, P. R., Malka, D., Rouleau, E., De Pauw, A., Buecher, B., Nogues, C., Fourme, E., Colas, C., Coulet, F., Warcoin, M., Grandjouan, S., Sezeur, A., Laurent-Puig, P., Moliere, D., Tlemsani, C., Di Maria, M., Byrde, V., Delaloge, S., Blayau, M., Caron, O. <strong>CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: a multicentre study.</strong> J. Med. Genet. 50: 486-489, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23709761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23709761</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-101472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23709761">Benusiglio et al. (2013)</a> found 16 different mutations, including 14 point mutations and 2 large deletions. Most of the mutations were truncating; 9 of the 16 mutations had not previously been reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23709761" 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="#1" class="mim-tip-reference" title="Benusiglio, P. R., Malka, D., Rouleau, E., De Pauw, A., Buecher, B., Nogues, C., Fourme, E., Colas, C., Coulet, F., Warcoin, M., Grandjouan, S., Sezeur, A., Laurent-Puig, P., Moliere, D., Tlemsani, C., Di Maria, M., Byrde, V., Delaloge, S., Blayau, M., Caron, O. <strong>CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: a multicentre study.</strong> J. Med. Genet. 50: 486-489, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23709761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23709761</a>] [<a href="https://doi.org/10.1136/jmedgenet-2012-101472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23709761">Benusiglio et al. (2013)</a> proposed using the name 'Hereditary Diffuse Gastric and Lobular Breast Cancer' for this disorder instead of HDGC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23709761" 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="#Correa1988" class="mim-tip-reference" title="Correa, P. <strong>A human model of gastric carcinogenesis.</strong> Cancer Res. 48: 3554-3560, 1988.">Correa (1988)</a>
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Benusiglio, P. R., Malka, D., Rouleau, E., De Pauw, A., Buecher, B., Nogues, C., Fourme, E., Colas, C., Coulet, F., Warcoin, M., Grandjouan, S., Sezeur, A., Laurent-Puig, P., Moliere, D., Tlemsani, C., Di Maria, M., Byrde, V., Delaloge, S., Blayau, M., Caron, O.
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<strong>CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: a multicentre study.</strong>
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J. Med. Genet. 50: 486-489, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23709761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23709761</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23709761" 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/10.1136/jmedgenet-2012-101472" target="_blank">Full Text</a>]
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Brooks-Wilson, A. R., Kaurah, P., Suriano, G., Leach, S., Senz, J., Grehan, N., Butterfield, Y. S. N., Jeyes, J., Schinas, J., Bacani, J., Kelsey, M., Ferreira, P., and 19 others.
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<strong>Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria.</strong>
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J. Med. Genet. 41: 508-517, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15235021/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15235021</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15235021" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Caldas, C., Carneiro, F., Lynch, H. T., Yokota, J., Wiesner, G. L., Powell, S. M., Lewis, F. R., Huntsman, D. G., Pharoah, P. D. P., Jankowski, J. A., MacLeod, P., Vogelsang, H., and 12 others.
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<strong>Familial gastric cancer: overview and guidelines for management.</strong>
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J. Med. Genet. 36: 873-880, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10593993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10593993</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10593993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Carneiro, F., Seixas, M., Sobrinho-Simoes, M.
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<strong>New elements for an updated classification of the carcinomas of the stomach.</strong>
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Path. Res. Pract. 191: 571-584, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7479380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7479380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7479380" 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/S0344-0338(11)80878-2" target="_blank">Full Text</a>]
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Chun, Y. S., Lindor, N. M., Smyrk, T. C., Petersen, B. T., Burgart, L. J., Guilford, P. J., Donohue, J. H.
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<strong>Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated?</strong>
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Cancer 92: 181-187, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11443625/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11443625</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11443625" 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/10.1002/1097-0142(20010701)92:1<181::aid-cncr1307>3.0.co;2-j" target="_blank">Full Text</a>]
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Correa, P.
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<strong>A human model of gastric carcinogenesis.</strong>
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Cancer Res. 48: 3554-3560, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3288329/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3288329</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3288329" 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/10.1136/jmg.2009.074237" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.2005.031385" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/79120" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/32918" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(1999)14:3<249::AID-HUMU8>3.0.CO;2-9" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJM200106213442504" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1159/000030069" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/apm.1965.64.1.31" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0165-4608(00)00273-9" target="_blank">Full Text</a>]
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Oliveira, C., Bordin, M. C., Grehan, N., Huntsman, D., Suriano, G., Machado, J. C., Kiviluoto, T., Aaltonen, L., Jackson, C. E., Seruca, R., Caldas, C.
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[<a href="https://doi.org/10.1002/humu.10068" target="_blank">Full Text</a>]
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Oliveira, C., Senz, J., Kaurah, P., Pinheiro, H., Sanges, R., Haegert, A., Corso, G., Schouten, J., Fitzgerald, R., Vogelsang, H., Keller, G., Dwerryhouse, S., and 9 others.
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[<a href="https://doi.org/10.1093/hmg/ddp046" target="_blank">Full Text</a>]
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Richards, F. M., McKee, S. A., Rajpar, M. H., Cole, T. R. P., Evans, D. G. R., Jankowski, J. A., McKeown, C., Sanders, D. S. A., Maher, E. R.
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[<a href="https://doi.org/10.1093/hmg/8.4.607" target="_blank">Full Text</a>]
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<a id="van der Post2015" class="mim-anchor"></a>
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van der Post, R. S., Vogelaar, I. P., Carneiro, F., Guilford, P., Huntsman, D., Hoogerbrugge, N., Caldas, C., Chelcun Schreiber, K. E., Hardwick, R. H., Ausems, M. G. E. M., Bardram, L., Benusiglio, P. R., and 36 others.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25979631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25979631</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25979631[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=25979631" 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/10.1136/jmedgenet-2015-103094" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 01/08/2016
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Cassandra L. Kniffin - updated : 7/23/2013<br>Cassandra L. Kniffin - updated : 12/3/2010<br>Cassandra L. Kniffin - updated : 11/29/2010<br>George E. Tiller - updated : 10/15/2009<br>Marla J. F. O'Neill - updated : 7/16/2008<br>Cassandra L. Kniffin - reorganized : 2/5/2008<br>Cassandra L. Kniffin - updated : 2/5/2008<br>Cassandra L. Kniffin - updated : 1/28/2008<br>Cassandra L. Kniffin - updated : 11/13/2007<br>Marla J. F. O'Neill - updated : 11/16/2006<br>Marla J. F. O'Neill - updated : 9/29/2005<br>Marla J. F. O'Neill - updated : 3/21/2005<br>Ada Hamosh - updated : 12/10/2004<br>Marla J. F. O'Neill - updated : 8/27/2004<br>Ada Hamosh - updated : 9/25/2003<br>Victor A. McKusick - updated : 3/5/2003<br>Victor A. McKusick - updated : 10/8/2002<br>Victor A. McKusick - updated : 10/9/2001<br>Michael J. Wright - updated : 3/9/2000<br>Wilson H. Y. Lo - updated : 12/2/1999<br>Victor A. McKusick - updated : 11/11/1999<br>Wilson H. Y. Lo - updated : 7/16/1999<br>Victor A. McKusick - updated : 6/18/1998
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Victor A. McKusick : 5/16/1990
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carol : 02/07/2022
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carol : 02/03/2022<br>carol : 08/12/2016<br>alopez : 01/08/2016<br>carol : 5/7/2015<br>carol : 7/24/2013<br>ckniffin : 7/23/2013<br>carol : 6/23/2011<br>carol : 12/22/2010<br>ckniffin : 12/21/2010<br>ckniffin : 12/3/2010<br>wwang : 11/30/2010<br>ckniffin : 11/29/2010<br>carol : 9/17/2010<br>wwang : 10/15/2009<br>terry : 10/15/2009<br>alopez : 6/3/2009<br>carol : 2/6/2009<br>alopez : 7/16/2008<br>carol : 3/18/2008<br>carol : 2/5/2008<br>ckniffin : 2/5/2008<br>carol : 2/5/2008<br>ckniffin : 2/5/2008<br>ckniffin : 2/5/2008<br>ckniffin : 1/28/2008<br>wwang : 11/27/2007<br>ckniffin : 11/13/2007<br>wwang : 11/17/2006<br>terry : 11/16/2006<br>wwang : 10/7/2005<br>terry : 9/29/2005<br>mgross : 4/14/2005<br>mgross : 4/13/2005<br>wwang : 3/21/2005<br>alopez : 12/14/2004<br>terry : 12/10/2004<br>carol : 8/27/2004<br>terry : 8/27/2004<br>alopez : 10/31/2003<br>tkritzer : 9/30/2003<br>terry : 9/25/2003<br>tkritzer : 3/19/2003<br>tkritzer : 3/11/2003<br>terry : 3/5/2003<br>carol : 10/29/2002<br>tkritzer : 10/17/2002<br>tkritzer : 10/8/2002<br>tkritzer : 10/8/2002<br>mcapotos : 11/15/2001<br>carol : 11/13/2001<br>mcapotos : 10/24/2001<br>terry : 10/9/2001<br>carol : 3/30/2000<br>alopez : 3/9/2000<br>carol : 12/3/1999<br>terry : 12/2/1999<br>carol : 11/11/1999<br>carol : 11/11/1999<br>carol : 11/11/1999<br>carol : 7/19/1999<br>carol : 7/16/1999<br>kayiaros : 6/28/1999<br>kayiaros : 6/28/1999<br>terry : 8/20/1998<br>carol : 6/19/1998<br>terry : 6/18/1998<br>mimadm : 9/24/1994<br>supermim : 3/16/1992<br>supermim : 5/16/1990
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<span class="mim-font">
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<strong>#</strong> 137215
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<h3>
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DIFFUSE GASTRIC AND LOBULAR BREAST CANCER SYNDROME; DGLBC
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<em>Alternative titles; symbols</em>
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GASTRIC CANCER, HEREDITARY DIFFUSE; HDGC<br />
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GASTRIC CANCER, FAMILIAL DIFFUSE BREAST CANCER, LOBULAR; LBC
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<span class="mim-font">
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Other entities represented in this entry:
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DIFFUSE GASTRIC AND LOBULAR BREAST CANCER SYNDROME WITH CLEFT LIP AND WITH OR WITHOUT CLEFT PALATE, INCLUDED
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<strong>ORPHA:</strong> 26106;
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<strong>DO:</strong> 0080764;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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16q22.1
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<span class="mim-font">
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Diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate
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<span class="mim-font">
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137215
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Autosomal dominant
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<span class="mim-font">
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3
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CDH1
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192090
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<span class="mim-font">
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<strong>TEXT</strong>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that diffuse gastric and lobular breast cancer syndrome (DGLBC) is caused by heterozygous germline mutation in the E-cadherin gene (CDH1; 192090) on chromosome 16q22.</p><p>Somatic mutation in the CDH1 gene has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer.</p>
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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 class="mim-text-font">
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<p>Diffuse gastric cancer and lobular breast cancer syndrome (DGLBC) is an autosomal dominant cancer predisposition syndrome. Heterozygous CDH1 mutation carriers have a 70 to 80% lifetime risk of developing diffuse gastric cancer. In addition to gastric cancer, up to 60% of female mutation carriers develop lobular carcinoma of the breast, and some carriers may develop colorectal cancer. Identification of mutation carriers is important, because the characteristic microscopic foci of signet ring cell adenocarcinoma in HDGC usually involves the submucosa and is often not readily detectable by routine upper endoscopy screening (summary by Fitzgerald et al., 2010). </p><p>DGLBC is considered to be a distinct disease entity from the more common sporadic occurrence of gastric cancer (613659), which can be associated with environmental factors such as Helicobacter pylori infection, high-fat diet, or smoking and is often associated with somatic mutations in disease tissue.</p>
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<strong>Clinical Features</strong>
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<p>Jones (1964) described 3 multigenerational Maori families from New Zealand segregating early-onset familial gastric cancer. These families were later studied in detail by Guilford et al. (1998). In 1 family, 25 members ranging in age from 14 years upwards had died over 30 years. The majority of cases occurred before age 40 years, which was in marked contrast to the general experience in New Zealand, where about 80% of gastric cancers occur in people older than 60 years. There was no evidence of an increased cancer rate of other organs in this family. Pathology showed histologically poorly differentiated, high-grade, diffuse gastric cancer. </p><p>Kakiuchi et al. (1999) studied the clinical features of the probands of 16 Japanese gastric cancer families, which was defined as the existence of 3 or more family members with gastric cancer in at least 2 successive generations. These patients developed cancers more frequently in the cardiac region of the stomach. In addition, the cancers were more often of the undifferentiated type, and were more frequently associated with disseminated peritoneal and liver metastases compared to sporadic cases. </p><p>Richards et al. (1999) reported a family from the U.K. in which 6 individuals developed diffuse gastric cancer. In addition to the 6 members with gastric cancer, 1 member of the family developed adenocarcinoma of the rectum at the age of 30 years. Genetic analysis identified a heterozygous mutation in the CDH1 gene (192090.0008). </p><p>Huntsman et al. (2001) described genetic screening, surgical management, and pathologic findings in young persons with truncating CDH1 mutations (192090.0012; 192090.0013) in 2 unrelated families with hereditary diffuse gastric cancer reported by Gayther et al. (1998). Total gastrectomy was performed prophylactically in 5 carriers of mutations who were between 22 and 40 years of age. In each case, superficial infiltrates of malignant signet ring cells were identified in surgical samples. </p><p>Chun et al. (2001) reported a family with a strong history of HDGC. Five family members, including a sister and brother and 3 first cousins, underwent endoscopic evaluations, which were negative for malignancy, and elected to undergo a prophylactic total gastrectomy with Roux-en-Y esophagojejunostomy. Intramucosal signet ring cell adenocarcinoma was found in various regions of the stomach in all 5 patients, and all 5 demonstrated diminished or absent E-cadherin reactivity in the cancerous mucosa. The age of the 5 patients at the time of surgery varied from 40 to 63 years. </p><p>Brooks-Wilson et al. (2004) reported 10 different families with hereditary gastric cancer who had germline mutations in the CDH1 gene. There were multiple cases of breast cancers, including pathologically confirmed lobular breast cancer, in these families. </p><p>In a retrospective study of French patients who underwent genetic testing for germline mutations in the CDH1 gene, Benusiglio et al. (2013) found that 18 (11%) of 165 index cases carried pathogenic mutations. Eleven of these patients had a personal or family history that fulfilled diagnostic criteria delineated by Fitzgerald et al. (2010) (see DIAGNOSIS). However, 7 remaining cases did not meet the HDGC criteria: 3 women had sporadic bilateral lobular breast cancer before age 50; 3 came from families with 2 cases of DGC after age 50; and 1 had sporadic diffuse gastric cancer after age 40. Of the 3 woman with LBC before age 50, 2 were only tested for CDH1 after subsequently developing symptomatic DGC and thus meeting the criteria. The remaining woman had CDH1 testing and prophylactic gastrectomy that revealed DGC despite a negative screening endoscopy. These findings suggested that early-onset LBC might be the first manifestation of HDGC, and that a personal or family history of multiple LBCs at a young age, even in the absence of DGC, should prompt cancer geneticists to test for CDH1 germline mutations. </p><p><strong><em>Diffuse Gastric and Lobular Breast Cancer Syndrome with or without Cleft Palate</em></strong></p><p>
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Frebourg et al. (2006) reported 2 unrelated families segregating diffuse gastric cancer and cleft palate. Genetic analysis confirmed that affected individuals with gastric cancer with or without cleft palate had heterozygous mutations in the CDH1 gene (192090.0019 and 192090.0020, respectively). In 1 family, 4 mutation carriers had diffuse gastric cancer and cleft lip/palate and 2 mutation carriers had gastric cancer without clefting. In the second family, a man and his 2 daughters had gastric cancer, a daughter with the mutation had cleft lip but no gastric cancer at age 25, and a 16-year-old son with the mutation had congenital aplasia cutis of the scalp and partial acrania (107600) but no known gastric cancer. Both mutations were splicing mutations generating aberrant transcripts with an in-frame deletion, removing the extracellular cadherin repeat domains involved in cell-cell adhesion. Such transcripts might encode mutant proteins with trans-dominant-negative effects. Expression of CDH1 in human embryos during critical stages of lip and palate development suggested that alteration of the E-cadherin pathway may contribute to human clefting. </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Diagnosis</strong>
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</h4>
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</div>
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<p>Caldas et al. (1999) reported the proceedings of the First Workshop of the International Gastric Cancer Linkage Consortium convened to produce consensus statements and guidelines for familial gastric cancer. Caldas et al. (1999) noted that review of pathologic samples from 8 families with inactivating germline mutations in the E-cadherin gene showed that all of the gastric cancers in these families were of diffuse type, and 2 of these had a glandular/intestinal component. Hereditary diffuse gastric cancer was defined as existing in any family in which there were (1) 2 or more documented cases of diffuse gastric cancer in first- or second-degree relatives with at least one cancer diagnosed before the age of 50; or (2) 3 or more cases of diffuse gastric cancer in first- or second-degree relatives independent of age of onset. Caldas et al. (1999) also noted that since 5 individuals below the age of 18 had developed diffuse gastric carcinoma, testing of minors might be justified. </p><p>Fitzgerald et al. (2010) presented updated consensus guidelines for HDGC, which included broadening of CDH1 testing criteria: histologic confirmation of diffuse gastric criteria is only required for 1 family member; inclusion of individuals with diffuse gastric cancer before the age of 40 years without a family history; and inclusion of individuals and families with diagnoses of both diffuse gastric cancer (including one before the age of 50 years) and lobular breast cancer. Large genomic rearrangements of CDH1 should be sought in addition to direct sequencing. </p><p>Benusiglio et al. (2013) suggested that the criteria for CDH1 testing put forth by Fitzgerald et al. (2010) may be too strict, and proposed that a personal or family history of 2 histologically proven lobular breast cancers before age 50, after exclusion of a germline mutation in BRCA1 and BRCA2, should be added to the criteria for CDH1 testing. </p><p>Van der Post et al. (2015) reported the results of a multidisciplinary workshop that discussed genetic testing and management of patients with hereditary diffuse gastric cancer (DGC). The workshop recommended that CDH1 testing criteria should take into account first and second-degree relatives: (1) families with 2 or more patients with gastric cancer at any age, 1 confirmed diffuse gastric cancer; (2) individuals with DGC before the age of 40 and (3) families with diagnoses of both DGC and lobular breast cancer (LBC), 1 diagnosis before the age of 50. Additionally, CDH1 testing could be considered in patients with bilateral or familial LBC before the age of 50, patients with DGC and cleft lip/palate, and those with precursor lesions for signet ring cell carcinoma. </p>
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</span>
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<div>
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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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</div>
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<span class="mim-text-font">
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<p>Fitzgerald et al. (2010) presented updated consensus guidelines for the genetic counseling, management, and surveillance of HDGC. They recommended strong consideration of prophylactic total gastrectomy in mutation-positive individuals or, at the least, detailed endoscopic surveillance with multiple biopsies. Annual mammography and breast MRI from the age of 35 years was recommended for women. </p><p>Lynch et al. (2000) described E-cadherin mutation-based genetic counseling in an affected kindred reported by Guilford et al. (1999). Of 24 family members tested for the familial mutation (192090.0011), 9 were found to be positive and 15 negative. None of the 19 patients counseled wanted results sent to their physicians once they recognized the potential for insurance discrimination. None had undergone endoscopic ultrasound. Three who were positive for the mutation expressed strong interest in prophylactic gastrectomy. Three of the 9 who tested positive were affected and had died by the time of report. </p><p>Van der Post et al. (2015) reported the results of a multidisciplinary workshop that discussed management of patients who test positive for CDH1 pathogenic variants related to diffuse gastric cancer. Given the high mortality associated with invasive disease, prophylactic total gastrectomy at a center of expertise was advised for individuals with pathogenic CDH1 mutations. Breast cancer surveillance with annual breast MRI starting at age 30 for women with a CDH1 mutation was recommended. Standardized endoscopic surveillance in experienced centers was recommended for those opting not to have gastrectomy, those with CDH1 variants of uncertain significance, and those that fulfill hereditary DGC criteria without germline CDH1 mutations. </p>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Diffuse gastric cancer and lobular breast cancer syndrome is an autosomal dominant cancer predisposition syndrome. Fitzgerald et al. (2010) reported that heterozygous CDH1 mutation carriers have a 70 to 80% lifetime risk of developing gastric cancer. In addition to gastric cancer, up to 60% of female mutation carriers will develop lobular carcinoma of the breast, and some carriers may develop colorectal cancer. </p>
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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>Lauren (1965) defined 2 main histologic types of gastric carcinomas, a 'diffuse' type and a so-called 'intestinal' type. Diffuse tumors, as observed in HDGC, are poorly differentiated infiltrating lesions resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease. This classification system was updated (Carneiro et al., 1995) to include 4 main types of gastric cancer: isolated cell and mixed types (representing the diffuse component); and glandular/intestinal and solid (representing the non-diffuse component). </p><p>In a review of HDGC from a consensus statement, Fitzgerald et al. (2010) noted that histologic study of prophylactic gastrectomies almost universally showed pre-invasive lesions, including in situ signet ring carcinoma with pagetoid spread of signet ring cells. </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>Mapping</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>By linkage analysis of a large New Zealand family with autosomal dominant inheritance of diffuse gastric cancer, Guilford et al. (1998) found significant linkage to chromosome 16q22.1 (maximum 2-point lod score of 5.04 at marker D16S752). Segregation of the disease haplotype indicated a penetrance of 70% by age 60 years. </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>Molecular 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>In affected members of 3 New Zealand families with HDGC, Guilford et al. (1998) identified heterozygous germline mutations in the CDH1 gene (192090.0005-192090.0007). </p><p>Grady et al. (2000) noted that patients with heterozygous germline mutations in the CDH1 gene develop gastric cancer, but their cancers consistently demonstrate no loss of heterozygosity (LOH) at the CDH1 locus. They hypothesized that methylation of the CDH1 promoter might represent the 'second genetic hit' in the genesis of these tumors. The CDH1 promoter was found to be consistently unmethylated in normal stomach mucosa, whereas 3 of 6 HDGC tumors with negative CDH1 staining had aberrant CDH1 promoter methylation. Two tumors that had retained unmethylated CDH1 promoters harbored somatic CDH1 mutations. No somatic mutations were found in 2 HDGC tumors showing CDH1 promoter methylation, but sequence polymorphisms confirmed that they retained a second wildtype allele. These findings indicated that the formation of HDGC tumors requires biallelic CDH1 inactivation, which in one-half of cases is accomplished by promoter methylation of a retained wildtype allele. </p><p>In a family with a strong history of diffuse gastric carcinoma, Chun et al. (2001) found a 1558insC germline mutation in the CDH1 gene (192090.0014). </p><p>Oliveira et al. (2002) performed germline CDH1 mutation screening in 39 kindreds with familial aggregation of gastric cancer, a subset of which fulfilled the criteria defined by the International Gastric Cancer Linkage Consortium (IGCLC) for hereditary diffuse gastric cancer. CDH1 germline mutations were detected in 4 of 11 (36.4%) HDGC families. No mutations were identified in 63.6% of HDGC families or in kindreds with familial aggregation of gastric cancer not fulfilling criteria for HDGC. These results added support to the evidence that only HDGC families harbor germline mutations in CDH1 and that genes other than CDH1 remained to be identified. </p><p>Among 43 apparent cases of hereditary gastric cancer, Brooks-Wilson et al. (2004) identified heterozygous mutations in the CDH1 gene in 10 different families. There were 10 loss-of-function mutations, including 2 insertions, 5 deletions, 2 splice site substitutions, and 1 complex deletion/insertion involving a splice site. They also found 3 heterozygous missense mutations that were predicted to affect conserved residues and to have deleterious effects on protein function. </p><p>Oliveira et al. (2009) reported 6 (6.5%) of 93 previously described mutation-negative hereditary diffuse gastric cancer probands who carried genomic deletions of the CDH1 gene (see, e.g., 192090.0022 and 192090.0023). The statistically significant overrepresentation of Alu repeats around breakpoints indicated nonhomologous allelic recombination of Alu repeats as a likely mechanism for these deletions. When all mutations and deletions were considered, the overall frequency of CDH1 alterations in HDGC was approximately 46% (73 of 160), and large CDH1 deletions occurred in 3.8% of HDGC families. </p><p>Among 18 index patients with germline CDH1 mutations identified retrospectively, Benusiglio et al. (2013) found 16 different mutations, including 14 point mutations and 2 large deletions. Most of the mutations were truncating; 9 of the 16 mutations had not previously been reported. </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>Nomenclature</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>Benusiglio et al. (2013) proposed using the name 'Hereditary Diffuse Gastric and Lobular Breast Cancer' for this disorder instead of HDGC. </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>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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Correa (1988)
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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>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Benusiglio, P. R., Malka, D., Rouleau, E., De Pauw, A., Buecher, B., Nogues, C., Fourme, E., Colas, C., Coulet, F., Warcoin, M., Grandjouan, S., Sezeur, A., Laurent-Puig, P., Moliere, D., Tlemsani, C., Di Maria, M., Byrde, V., Delaloge, S., Blayau, M., Caron, O.
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<strong>CDH1 germline mutations and the hereditary diffuse gastric and lobular breast cancer syndrome: a multicentre study.</strong>
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J. Med. Genet. 50: 486-489, 2013.
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[Full Text: https://doi.org/10.1136/jmedgenet-2012-101472]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Brooks-Wilson, A. R., Kaurah, P., Suriano, G., Leach, S., Senz, J., Grehan, N., Butterfield, Y. S. N., Jeyes, J., Schinas, J., Bacani, J., Kelsey, M., Ferreira, P., and 19 others.
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<strong>Germline E-cadherin mutations in hereditary diffuse gastric cancer: assessment of 42 new families and review of genetic screening criteria.</strong>
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J. Med. Genet. 41: 508-517, 2004.
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[Full Text: https://doi.org/10.1136/jmg.2004.018275]
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<p class="mim-text-font">
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Caldas, C., Carneiro, F., Lynch, H. T., Yokota, J., Wiesner, G. L., Powell, S. M., Lewis, F. R., Huntsman, D. G., Pharoah, P. D. P., Jankowski, J. A., MacLeod, P., Vogelsang, H., and 12 others.
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<strong>Familial gastric cancer: overview and guidelines for management.</strong>
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J. Med. Genet. 36: 873-880, 1999.
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<p class="mim-text-font">
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Carneiro, F., Seixas, M., Sobrinho-Simoes, M.
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<strong>New elements for an updated classification of the carcinomas of the stomach.</strong>
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Path. Res. Pract. 191: 571-584, 1995.
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</p>
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<li>
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<p class="mim-text-font">
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Chun, Y. S., Lindor, N. M., Smyrk, T. C., Petersen, B. T., Burgart, L. J., Guilford, P. J., Donohue, J. H.
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<strong>Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated?</strong>
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Cancer 92: 181-187, 2001.
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</p>
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<li>
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<p class="mim-text-font">
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Correa, P.
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<strong>A human model of gastric carcinogenesis.</strong>
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Cancer Res. 48: 3554-3560, 1988.
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[PubMed: 3288329]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Fitzgerald, R. C., Hardwick, R., Huntsman, D., Carneiro, F., Guilford, P., Blair, V., Chung, D. C., Norton, J., Ragunath, K., Van Grieken, N. C., Dwerryhouse, S., Caldas, C., International Gastric Cancer Linkage Consortium.
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<strong>Hereditary diffuse gastric cancer: updated consensus guidelines for clinical management and directions for future research.</strong>
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J. Med. Genet. 47: 436-444, 2010. Note: Erratum: J. Med. Genet. 48: 216 only, 2011.
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[PubMed: 20591882]
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[Full Text: https://doi.org/10.1136/jmg.2009.074237]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Frebourg, T., Oliveira, C., Hochain, P., Karam, R., Manouvrier, S., Graziadio, C., Vekemans, M., Hartmann, A., Baert-Desurmont, S., Alexandre, C., Lejeune Dumoulin, S., Marroni, C., and 16 others.
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<strong>Cleft lip/palate and CDH1/E-cadherin mutation in families with hereditary diffuse gastric cancer.</strong>
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J. Med. Genet. 43: 138-142, 2006.
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[PubMed: 15831593]
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[Full Text: https://doi.org/10.1136/jmg.2005.031385]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Gayther, S. A., Gorringe, K. L., Ramus, S. J., Huntsman, D., Roviello, F., Grehan, N., Machado, J. C., Pinto, E., Seruca, R., Halling, K., MacLeod, P., Powell, S. M., Jackson, C. E., Ponder, B. A. J., Caldas, C.
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<strong>Identification of germ-line E-cadherin mutations in gastric cancer families of European origin.</strong>
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Cancer Res. 58: 4086-4089, 1998.
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[PubMed: 9751616]
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</li>
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<li>
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<p class="mim-text-font">
|
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Grady, W. M., Willis, J., Guilford, P. J., Dunbier, A. K., Toro, T. T., Lynch, H., Wiesner, G., Ferguson, K., Eng, C., Park, J.-G., Kim, S.-J., Markowitz, S.
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<strong>Methylation of the CDH1 promoter as the second genetic hit in hereditary diffuse gastric cancer.</strong>
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Nature Genet. 26: 16-17, 2000.
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[PubMed: 10973239]
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[Full Text: https://doi.org/10.1038/79120]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Guilford, P., Hopkins, J., Harraway, J., McLeod, M., McLeod, N., Harawira, P., Taite, H., Scoular, R., Miller, A., Reeve, A. E.
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<strong>E-cadherin germline mutations in familial gastric cancer.</strong>
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Nature 392: 402-405, 1998.
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[PubMed: 9537325]
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[Full Text: https://doi.org/10.1038/32918]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Guilford, P. J., Hopkins, J. B. W., Grady, W. M., Markowitz, S. D., Willis, J., Lynch, H., Rajput, A., Wiesner, G. L., Lindor, N. M., Burgart, L. J., Toro, T. T., Lee, D., Limacher, J.-M., Shaw, D. W., Findlay, M. P. N., Reeve, A. E.
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<strong>E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer.</strong>
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Hum. Mutat. 14: 249-255, 1999.
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[PubMed: 10477433]
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[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1999)14:3<249::AID-HUMU8>3.0.CO;2-9]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Huntsman, D. G., Carneiro, F., Lewis, F. R., MacLeod, P. M., Hayashi, A., Monaghan, K. G., Maung, R., Seruca, R., Jackson, C. E., Caldas, C.
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<strong>Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations.</strong>
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New Eng. J. Med. 344: 1904-1909, 2001.
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</p>
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<li>
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<p class="mim-text-font">
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Jones, E. G.
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<strong>Familial gastric cancer.</strong>
|
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New Zealand Med. J. 63: 287-296, 1964.
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[PubMed: 14158754]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Kakiuchi, H., Itoh, F., Kusano, M., Adachi, Y., Mita, H., Mihara, M., Matsuno, K., Endo, T., Hinoda, Y., Hosokawa, M., Imai, K.
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<strong>Familial gastric cancer in the Japanese population is frequently located at the cardiac region.</strong>
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Tumour Biol. 20: 235-241, 1999.
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[PubMed: 10436415]
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[Full Text: https://doi.org/10.1159/000030069]
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</p>
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<li>
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<p class="mim-text-font">
|
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Lauren, P.
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<strong>The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification.</strong>
|
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Acta Path. Microbiol. Scand. 64: 31-49, 1965.
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[PubMed: 14320675]
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[Full Text: https://doi.org/10.1111/apm.1965.64.1.31]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Lynch, H. T., Grady, W., Lynch, J. F., Tsuchiya, K. D., Wiesner, G., Markowitz, S. D.
|
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<strong>E-cadherin mutation-based genetic counseling and hereditary diffuse gastric carcinoma.</strong>
|
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Cancer Genet. Cytogenet. 122: 1-6, 2000.
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[PubMed: 11104024]
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[Full Text: https://doi.org/10.1016/s0165-4608(00)00273-9]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Oliveira, C., Bordin, M. C., Grehan, N., Huntsman, D., Suriano, G., Machado, J. C., Kiviluoto, T., Aaltonen, L., Jackson, C. E., Seruca, R., Caldas, C.
|
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<strong>Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred.</strong>
|
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Hum. Mutat. 19: 510-517, 2002.
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[PubMed: 11968083]
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[Full Text: https://doi.org/10.1002/humu.10068]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Oliveira, C., Senz, J., Kaurah, P., Pinheiro, H., Sanges, R., Haegert, A., Corso, G., Schouten, J., Fitzgerald, R., Vogelsang, H., Keller, G., Dwerryhouse, S., and 9 others.
|
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<strong>Germline CDH1 deletions in hereditary diffuse gastric cancer families.</strong>
|
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Hum. Molec. Genet. 18: 1545-1555, 2009.
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[PubMed: 19168852]
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[Full Text: https://doi.org/10.1093/hmg/ddp046]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Richards, F. M., McKee, S. A., Rajpar, M. H., Cole, T. R. P., Evans, D. G. R., Jankowski, J. A., McKeown, C., Sanders, D. S. A., Maher, E. R.
|
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<strong>Germline E-cadherin gene (CDH1) mutations predispose to familial gastric cancer and colorectal cancer.</strong>
|
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Hum. Molec. Genet. 8: 607-610, 1999.
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[PubMed: 10072428]
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[Full Text: https://doi.org/10.1093/hmg/8.4.607]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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van der Post, R. S., Vogelaar, I. P., Carneiro, F., Guilford, P., Huntsman, D., Hoogerbrugge, N., Caldas, C., Chelcun Schreiber, K. E., Hardwick, R. H., Ausems, M. G. E. M., Bardram, L., Benusiglio, P. R., and 36 others.
|
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<strong>Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers.</strong>
|
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J. Med. Genet. 52: 361-374, 2015.
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[PubMed: 25979631]
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[Full Text: https://doi.org/10.1136/jmedgenet-2015-103094]
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</p>
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</li>
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</ol>
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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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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 01/08/2016<br>Cassandra L. Kniffin - updated : 7/23/2013<br>Cassandra L. Kniffin - updated : 12/3/2010<br>Cassandra L. Kniffin - updated : 11/29/2010<br>George E. Tiller - updated : 10/15/2009<br>Marla J. F. O'Neill - updated : 7/16/2008<br>Cassandra L. Kniffin - reorganized : 2/5/2008<br>Cassandra L. Kniffin - updated : 2/5/2008<br>Cassandra L. Kniffin - updated : 1/28/2008<br>Cassandra L. Kniffin - updated : 11/13/2007<br>Marla J. F. O'Neill - updated : 11/16/2006<br>Marla J. F. O'Neill - updated : 9/29/2005<br>Marla J. F. O'Neill - updated : 3/21/2005<br>Ada Hamosh - updated : 12/10/2004<br>Marla J. F. O'Neill - updated : 8/27/2004<br>Ada Hamosh - updated : 9/25/2003<br>Victor A. McKusick - updated : 3/5/2003<br>Victor A. McKusick - updated : 10/8/2002<br>Victor A. McKusick - updated : 10/9/2001<br>Michael J. Wright - updated : 3/9/2000<br>Wilson H. Y. Lo - updated : 12/2/1999<br>Victor A. McKusick - updated : 11/11/1999<br>Wilson H. Y. Lo - updated : 7/16/1999<br>Victor A. McKusick - updated : 6/18/1998
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Victor A. McKusick : 5/16/1990
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