2732 lines
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Entry
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- #155240 - THYROID CARCINOMA, FAMILIAL MEDULLARY; MTC
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- OMIM
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<p>
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<span class="h4">#155240</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/155240"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#otherFeatures">Other Features</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#clinicalManagement">Clinical Management</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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<li role="presentation">
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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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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=THYROID CARCINOMA, FAMILIAL MEDULLARY" 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="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
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<div id="mimEuroGentestFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=906&Typ=Pat" title="Multiple endocrine neoplasia type 2" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Multiple endocrine neoplas… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=14205&Typ=Pat" title="Familial medullary thyroid carcinoma" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Familial medullary thyroid… </a></div>
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</div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1257/" 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.ncbi.nlm.nih.gov/gtr/all/tests/?term=155240[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="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
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<div id="mimOrphanetFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=653" title="Multiple endocrine neoplasia type 2" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Multiple endocrine neoplas…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=99361" title="Familial medullary thyroid carcinoma" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Familial medullary thyroid…</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0050547" 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/155240" 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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<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="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>ORPHA:</strong> 653, 99361<br />
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<strong>DO:</strong> 0050547<br />
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">ICD+</a>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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155240
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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THYROID CARCINOMA, FAMILIAL MEDULLARY; MTC
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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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FMTC<br />
|
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MTC1
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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="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/10/158?start=-3&limit=10&highlight=158">
|
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10q11.21
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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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Medullary thyroid carcinoma
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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/155240"> 155240 </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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<a href="/entry/164761"> 164761 </a>
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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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- Medullary thyroid carcinoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1332275004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1332275004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/255032005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">255032005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238462&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238462</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002865" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002865</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002865" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002865</a>]</span><br /> - No other primary tumors<br />
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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 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.">
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<p>A number sign (#) is used with this entry because of evidence that familial MTC occurs from mutation in the RET gene (<a href="/entry/164761">164761</a>) on chromosome 10. Familial MTC can also be caused by mutations in the NTRK1 gene (<a href="/entry/191315">191315</a>) located on 1q21-q22.</p>
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<p>Medullary thyroid carcinoma (MTC) is a malignant tumor of the calcitonin (<a href="/entry/114130">114130</a>)-secreting parafollicular C cells of the thyroid, and occurs sporadically or as a component of the multiple endocrine neoplasia (MEN) type 2 (see <a href="/entry/171400">171400</a>)/familial medullary thyroid carcinoma (FMTC) syndromes (summary by <a href="#1" class="mim-tip-reference" title="Abu-Amero, K. K., Alzahrani, A. S., Zou, M., Shi, Y. <strong>Association of mitochondrial DNA transversion mutations with familial medullary thyroid carcinoma/multiple endocrine neoplasia type 2 syndrome.</strong> Oncogene 25: 677-684, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16205644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16205644</a>] [<a href="https://doi.org/10.1038/sj.onc.1209094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16205644">Abu-Amero et al., 2006</a>). Thyroid cancer derived from follicular epithelial cells is referred to as nonmedullary thyroid cancer and comprises several subtypes; see <a href="/entry/188550">188550</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16205644" 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>About 75% of medullary thyroid carcinoma is sporadic; these cases are unilateral. Bilateral multifocal medullary carcinoma is a cardinal feature of autosomal dominant multiple endocrine neoplasia type II (MEN2A; <a href="/entry/171400">171400</a>). In addition, there are cases of familial medullary thyroid carcinoma in which there are no extrathyroid manifestations of multiple endocrine neoplasia; otherwise the behavior of the tumor is the same as that in the hereditary disease. Such families were observed by <a href="#5" class="mim-tip-reference" title="Farndon, J. R., Leight, G. S., Dilley, W. G., Baylin, S. B., Smallridge, R. C., Harrison, T. S., Wells, S. A., Jr. <strong>Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity.</strong> Brit. J. Surg. 73: 278-281, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3697657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3697657</a>] [<a href="https://doi.org/10.1002/bjs.1800730411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3697657">Farndon et al. (1986)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3697657" 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>Primary localized cutaneous amyloidosis (PLCA), which has been observed with MEN2A, was reported also in a family in which multiple affected members had an association only with medullary thyroid carcinoma (<a href="#6" class="mim-tip-reference" title="Ferrer, J. P., Halperin, I., Conget, J. I., Alsina, M., Martinez-Osaba, M. J., Palou, J., Bombi, J. A., Vilardell, E. <strong>Primary localized cutaneous amyloidosis and familial medullary thyroid carcinoma.</strong> Clin. Endocr. 34: 435-439, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1889128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1889128</a>] [<a href="https://doi.org/10.1111/j.1365-2265.1991.tb00322.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1889128">Ferrer et al., 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1889128" 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="Rakover, Y., Dharan, M., Luboshitsky, R. <strong>Hirschsprung's disease associated with isolated familial medullary carcinoma of the thyroid.</strong> J. Pediat. Endocr. 7: 373-377, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7735379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7735379</a>] [<a href="https://doi.org/10.1515/jpem.1994.7.4.373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7735379">Rakover et al. (1994)</a> described 2 sibs in whom isolated familial medullary carcinoma of the thyroid was diagnosed at the ages of 16 and 19 years. Hirschsprung disease was identified at the age of 1 year in both of them. Twelve other members of the family had medullary carcinoma of the thyroid. The authors stated that, although this was the first report of an association between Hirschsprung disease and isolated familial medullary carcinoma of the thyroid, the association should not be surprising because of the known association of both with mutations in the RET gene (<a href="/entry/164761">164761</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7735379" 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>Lore et al. (<a href="#9" class="mim-tip-reference" title="Lore, F., Di Cairano, G., Talidis, F. <strong>Unilateral renal agenesis in a family with medullary thyroid carcinoma. (Letter)</strong> New Eng. J. Med. 342: 1218-1219, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10777380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10777380</a>] [<a href="https://doi.org/10.1056/NEJM200004203421615" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10777380">2000</a>, <a href="#10" class="mim-tip-reference" title="Lore, F., Talidis, F., Di Cairano, G., Renieri, A. <strong>Multiple endocrine neoplasia type 2 syndromes may be associated with renal malformations.</strong> J. Intern. Med. 250: 37-42, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11454140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11454140</a>] [<a href="https://doi.org/10.1046/j.1365-2796.2001.00846.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11454140">2001</a>) described a 4-generation family with medullary thyroid carcinoma associated with a heterozygous RET mutation (C620S; <a href="/entry/164761#0041">164761.0041</a>). One of these individuals was found to have absence of the left kidney. Her son was found to have Hirschsprung disease (<a href="/entry/142623">142623</a>) at a few months of age and had undergone surgical resection of the involved intestinal segment. Subsequently, he was found to have the RET mutation and at the age of 15 years underwent total thyroidectomy, which revealed medullary thyroid carcinoma. Abnormal ultrasonography revealed the absence of the left kidney in the son also. No renal abnormalities were found on abdominal ultrasonography of the other living members. <a href="#10" class="mim-tip-reference" title="Lore, F., Talidis, F., Di Cairano, G., Renieri, A. <strong>Multiple endocrine neoplasia type 2 syndromes may be associated with renal malformations.</strong> J. Intern. Med. 250: 37-42, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11454140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11454140</a>] [<a href="https://doi.org/10.1046/j.1365-2796.2001.00846.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11454140">Lore et al. (2001)</a> concluded that MEN2 syndromes may be associated with renal malformations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11454140+10777380" 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 RT-PCR, <a href="#12" class="mim-tip-reference" title="Maio, M., Coral, S., Sigalotti, L., Elisei, R., Romei, C., Rossi, G., Cortini, E., Colizzi, F., Fenzi, G., Altomonte, M., Pinchera, A., Vitale, M. <strong>Analysis of cancer/testis antigens in sporadic medullary thyroid carcinoma: expression and humoral response to NY-ESO-1.</strong> J. Clin. Endocr. Metab. 88: 748-754, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574209</a>] [<a href="https://doi.org/10.1210/jc.2002-020830" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12574209">Maio et al. (2003)</a> examined the expression of a number of genes encoding cancer/testis antigens (CTAs) in 23 surgical samples of sporadic MTC. Of 11 cDNA antigens examined, NYESO1 (<a href="/entry/300156">300156</a>) cDNA was the most frequent, being detected in 15 of 23 examined samples (65.2%). NYESO1 expression in primary MTC tissues significantly correlated with tumor recurrence. The presence of specific anti-NYESO1 antibodies was searched in the sera of MTC-affected patients examined by ELISA using recombinant NYESO1 protein. A humoral response against this CTA was detected in 6 of 11 NYESO1-expressing patients (54.5%), and in 1 of 6 patients with an NYESO1-negative tumor. Anti-NYESO1 antibodies were present in 15 of 42 sera (35.7%), demonstrating that MTC is a neoplasm frequently associated with humoral immune response to NYESO1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574209" 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="#11" class="mim-tip-reference" title="Machens, A., Niccoli-Sire, P., Hoegel, J., Frank-Raue, K., van Vroonhoven, T. J., Roeher, H.-D., Wahl, R. A., Lamesch, P., Raue, F., Conte-Devolx, B., Dralle, H. <strong>Early malignant progression of hereditary medullary thyroid cancer.</strong> New Eng. J. Med. 349: 1517-1525, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14561794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14561794</a>] [<a href="https://doi.org/10.1056/NEJMoa012915" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14561794">Machens et al. (2003)</a> conducted a European multicenter study in which patients who had a RET point mutation in the germline were 20 years of age or younger, were asymptomatic, and had undergone total thyroidectomy after confirmation of the RET mutation. Altogether, 207 patients from 145 families were identified. There was a significant age-related progression from C cell hyperplasia to medullary thyroid carcinoma and, ultimately, lymph node metastasis in patients whose RET mutations were grouped according to the extracellular- and intracellular-domain codons affected and in those with mutations at codon 634 (e.g., <a href="/entry/164761#0003">164761.0003</a>). No lymph node metastases were noted in patients younger than 14 years. The age-related penetrance was unaffected by the type of amino acid substitution encoded by the various codon 634 mutations. The codon-specific differences in the age at presentation of cancer and the familial rates of concomitant adrenal and parathyroid involvement suggested that the risk of progression was based on the transforming potential of the individual RET mutations. These data provided initial guidelines for the timing of prophylactic thyroidectomy in asymptomatic carriers of RET gene mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14561794" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Cote, G. J., Gagel, R. F. <strong>Lessons learned from the management of a rare genetic cancer. (Editorial)</strong> New Eng. J. Med. 349: 1566-1568, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14561800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14561800</a>] [<a href="https://doi.org/10.1056/NEJMe038148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14561800">Cote and Gagel (2003)</a> provided an optimistic review of the management of familial medullary thyroid carcinoma. They diagrammed the extracellular, transmembrane, and intracellular portions of the RET gene and presented a graph of the earliest reported age at onset of MTC according to the specific mutated RET codon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14561800" 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>The linkage studies of <a href="#14" class="mim-tip-reference" title="Narod, S. A., Sobol, H., Nakamura, Y., Calmettes, C., Baulieu, J.-L., Bigorgne, J.-C., Chabrier, G., Couette, J., de Gennes, J. L., Duprey, J., Gardet, P., Guillausseau, P.-J., Guilloteau, D., Houdent, C., Lefebvre, J., Modigliani, E., Parmentier, C., Pugeat, M., Siame, C., Tourniaire, J., Vandroux, J.-C., Vinot, J.-M., Lenoir, G. M. <strong>Linkage analysis of hereditary thyroid carcinoma with and without pheochromocytoma.</strong> Hum. Genet. 83: 353-358, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2572534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2572534</a>] [<a href="https://doi.org/10.1007/BF00291380" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2572534">Narod et al. (1989)</a> appear to indicate conclusively that familial medullary carcinoma of the thyroid (without pheochromocytoma) is caused by an allele in the same gene that is the site of the mutation in MEN2. They studied 18 families, 9 with MEN2 and 9 with medullary carcinoma of the thyroid without pheochromocytoma, with probes specific for the pericentromeric region of chromosome 10 and found close linkage in both cases. Genetic heterogeneity of the susceptibility locus was not observed. The genetic mutation for medullary carcinoma was in disequilibrium with alleles of 2 closely linked marker loci. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2572534" 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 2 large families with medullary thyroid carcinoma (MTC1), <a href="#8" class="mim-tip-reference" title="Lairmore, T. C., Howe, J. R., Korte, J. A., Dilley, W. G., Aine, L., Aine, E., Wells, S. A., Jr., Donis-Keller, H. <strong>Familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2B map to the same region of chromosome 10 as multiple endocrine neoplasia type 2A.</strong> Genomics 9: 181-192, 1991. Note: Erratum: Genomics 10: 514 only, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1672289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1672289</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90237-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1672289">Lairmore et al. (1991)</a> showed that the maximum lod score between the neoplasia and marker D10Z1 was 5.88 with 0% recombination. They found no evidence for genetic heterogeneity among families with medullary thyroid carcinoma, MEN2B (<a href="/entry/162300">162300</a>), or MEN2A. The mutations causing these disorders thus appear to be related to each other as alleles. On the other hand, <a href="#3" class="mim-tip-reference" title="Carson, N. L., Simpson, N. E., Myers, S., Anderson, L., Clarke, C., Simpson, W. J., Bridge, P. J. <strong>Genetic heterogeneity in families with familial medullary thyroid carcinoma. (Abstract)</strong> Cytogenet. Cell Genet. 58: 1948 only, 1991."None>Carson et al. (1991)</a> reported 2 families in which the MTC mutation appeared not to be linked to the pericentromeric markers on chromosome 10. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1672289" 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="Gimm, O., Greco, A., Hoang-Vu, C., Dralle, H., Pierotti, M. A., Eng, C. <strong>Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma.</strong> J. Clin. Endocr. Metab. 84: 2784-2787, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10443680/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10443680</a>] [<a href="https://doi.org/10.1210/jcem.84.8.5901" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10443680">Gimm et al. (1999)</a> used SSCP analysis of 16 exons of NTRK1 (<a href="/entry/191315">191315</a>) from 31 sporadic MTCs and observed variants in 5 exons (exons 4 and 14-17). Sequence analysis demonstrated 1 sequence variant each in exons 4, 14, 16, and 17, and 4 different variants in exon 15. Differential restriction enzyme digestion specific for each variant confirmed the sequencing results. All variants were also present in the corresponding germline DNA. Interestingly, the sequence variants at codon 604 (C1810T; <a href="/entry/191315#0008">191315.0008</a>) and codon 613 (G1838T; <a href="/entry/191315#0009">191315.0009</a>) of exon 15 always occurred together, possibly representing linkage disequilibrium. The frequencies of the sequence variants in germline DNA from patients with sporadic MTC did not differ significantly from those in a race-matched control group. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10443680" 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="Marsh, D. J., Theodosopoulos, G., Martin-Schulte, K., Richardson, A.-L., Philips, J., Roher, H.-D., Delbridge, L., Robinson, B. G. <strong>Genome-wide copy number imbalances identified in familial and sporadic medullary thyroid carcinoma.</strong> J. Clin. Endocr. Metab. 88: 1866-1872, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12679485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12679485</a>] [<a href="https://doi.org/10.1210/jc.2002-021155" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12679485">Marsh et al. (2003)</a> identified chromosomal imbalances that occur in MTC including deletions of chromosomes 1p, 3q26.3-q27, 4, 9q13-q22, 13q, and 22q and amplifications of chromosome 19. These regions house known tumor suppressor genes as well as genes encoding subunits of the multicomponent complex of glycosylphosphatidylinositol-linked proteins (glial cell line-derived neurotrophic factor family receptors alpha-2-4; see <a href="/entry/601496">601496</a>) and their ligands glial cell line-derived neurotrophic factor (<a href="/entry/600837">600837</a>), neurturin (<a href="/entry/602018">602018</a>), persephin (<a href="/entry/602921">602921</a>), and artemin (<a href="/entry/603886">603886</a>) that facilitate RET dimerization and downstream signaling. Chromosomal imbalances in the MTC cell line TT were largely identical to those identified in primary MTC tumors, consolidating its use as a model for studying MTC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12679485" 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="Abu-Amero, K. K., Alzahrani, A. S., Zou, M., Shi, Y. <strong>Association of mitochondrial DNA transversion mutations with familial medullary thyroid carcinoma/multiple endocrine neoplasia type 2 syndrome.</strong> Oncogene 25: 677-684, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16205644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16205644</a>] [<a href="https://doi.org/10.1038/sj.onc.1209094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16205644">Abu-Amero et al. (2006)</a> identified nonsynonymous germline mitochondrial DNA (mtDNA) mutations in both normal and tumor tissue from 20 (76.9%) of 26 cases of medullary thyroid carcinoma, including 9 (69.2%) of 13 sporadic cases and 11 (84.6%) of 13 familial cases; 10 of 13 familial cases were patients with MEN2. The familial cases tended to have transversion mtDNA mutations rather than transition mutations. All 13 familial cases also had germline RET mutations. <a href="#1" class="mim-tip-reference" title="Abu-Amero, K. K., Alzahrani, A. S., Zou, M., Shi, Y. <strong>Association of mitochondrial DNA transversion mutations with familial medullary thyroid carcinoma/multiple endocrine neoplasia type 2 syndrome.</strong> Oncogene 25: 677-684, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16205644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16205644</a>] [<a href="https://doi.org/10.1038/sj.onc.1209094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16205644">Abu-Amero et al. (2006)</a> suggested that mtDNA mutations may be involved in medullary thyroid carcinoma tumorigenesis and/or progression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16205644" 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>Reclassified Variants</em></strong></p><p>
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The Y791F variant (<a href="/entry/164761#0034">164761.0034</a>) in the RET gene that was identified in patients with familial medullary thyroid carcinoma by <a href="#2" class="mim-tip-reference" title="Baumgartner-Parzer, S. M., Lang, R., Wagner, L., Heinze, G., Niederle, B., Kaserer, K., Waldhausl, W., Vierhapper, H. <strong>Polymorphisms in exon 13 and intron 14 of the RET protooncogene: genetic modifiers of medullary thyroid carcinoma?</strong> J. Clin. Endocr. Metab. 90: 6232-6236, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16118333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16118333</a>] [<a href="https://doi.org/10.1210/jc.2005-1278" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16118333">Baumgartner-Parzer et al. (2005)</a> has been reclassified as a variant of unknown significance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16118333" 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="Simpson, N. E. <strong>Personal Communication.</strong> Kingston, Ontario, Canada 9/3/1991."None>Simpson (1991)</a> proposed a branching classification of the forms of medullary thyroid carcinoma (MTC). MTC has 2 forms: MTC1 (with no other primary tumors) and MEN2. MEN2 has 2 forms: MEN2A and MEN2B. MEN2A has 3 forms: MEN2A-1 (MTC with pheochromocytoma and parathyroid tumor), MEN2A-2 (MTC with pheochromocytoma), and MEN2A-3 (MTC with parathyroid tumor).</p>
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Abu-Amero, K. K., Alzahrani, A. S., Zou, M., Shi, Y.
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<strong>Association of mitochondrial DNA transversion mutations with familial medullary thyroid carcinoma/multiple endocrine neoplasia type 2 syndrome.</strong>
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Oncogene 25: 677-684, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16205644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16205644</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16205644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Polymorphisms in exon 13 and intron 14 of the RET protooncogene: genetic modifiers of medullary thyroid carcinoma?</strong>
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J. Clin. Endocr. Metab. 90: 6232-6236, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16118333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16118333</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16118333" 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/10.1210/jc.2005-1278" target="_blank">Full Text</a>]
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<strong>Genetic heterogeneity in families with familial medullary thyroid carcinoma. (Abstract)</strong>
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Cytogenet. Cell Genet. 58: 1948 only, 1991.
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New Eng. J. Med. 349: 1566-1568, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14561800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14561800</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14561800" 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/10.1056/NEJMe038148" target="_blank">Full Text</a>]
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Farndon, J. R., Leight, G. S., Dilley, W. G., Baylin, S. B., Smallridge, R. C., Harrison, T. S., Wells, S. A., Jr.
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<strong>Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity.</strong>
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Brit. J. Surg. 73: 278-281, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3697657/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3697657</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3697657" 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/bjs.1800730411" target="_blank">Full Text</a>]
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</p>
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<a id="6" class="mim-anchor"></a>
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<a id="Ferrer1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ferrer, J. P., Halperin, I., Conget, J. I., Alsina, M., Martinez-Osaba, M. J., Palou, J., Bombi, J. A., Vilardell, E.
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<strong>Primary localized cutaneous amyloidosis and familial medullary thyroid carcinoma.</strong>
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Clin. Endocr. 34: 435-439, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1889128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1889128</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1889128" 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/10.1111/j.1365-2265.1991.tb00322.x" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
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<a id="Gimm1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Gimm, O., Greco, A., Hoang-Vu, C., Dralle, H., Pierotti, M. A., Eng, C.
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<strong>Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma.</strong>
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J. Clin. Endocr. Metab. 84: 2784-2787, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10443680/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10443680</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10443680" 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/10.1210/jcem.84.8.5901" target="_blank">Full Text</a>]
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</p>
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<a id="8" class="mim-anchor"></a>
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<a id="Lairmore1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Lairmore, T. C., Howe, J. R., Korte, J. A., Dilley, W. G., Aine, L., Aine, E., Wells, S. A., Jr., Donis-Keller, H.
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|
<strong>Familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2B map to the same region of chromosome 10 as multiple endocrine neoplasia type 2A.</strong>
|
|
Genomics 9: 181-192, 1991. Note: Erratum: Genomics 10: 514 only, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1672289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1672289</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1672289" 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/10.1016/0888-7543(91)90237-9" target="_blank">Full Text</a>]
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Lore2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Lore, F., Di Cairano, G., Talidis, F.
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<strong>Unilateral renal agenesis in a family with medullary thyroid carcinoma. (Letter)</strong>
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New Eng. J. Med. 342: 1218-1219, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10777380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10777380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10777380" 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/10.1056/NEJM200004203421615" target="_blank">Full Text</a>]
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<a id="Lore2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Lore, F., Talidis, F., Di Cairano, G., Renieri, A.
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<strong>Multiple endocrine neoplasia type 2 syndromes may be associated with renal malformations.</strong>
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J. Intern. Med. 250: 37-42, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11454140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11454140</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11454140" 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/10.1046/j.1365-2796.2001.00846.x" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
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<a id="Machens2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Machens, A., Niccoli-Sire, P., Hoegel, J., Frank-Raue, K., van Vroonhoven, T. J., Roeher, H.-D., Wahl, R. A., Lamesch, P., Raue, F., Conte-Devolx, B., Dralle, H.
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<strong>Early malignant progression of hereditary medullary thyroid cancer.</strong>
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New Eng. J. Med. 349: 1517-1525, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14561794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14561794</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14561794" 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/10.1056/NEJMoa012915" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
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<a id="Maio2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Maio, M., Coral, S., Sigalotti, L., Elisei, R., Romei, C., Rossi, G., Cortini, E., Colizzi, F., Fenzi, G., Altomonte, M., Pinchera, A., Vitale, M.
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<strong>Analysis of cancer/testis antigens in sporadic medullary thyroid carcinoma: expression and humoral response to NY-ESO-1.</strong>
|
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J. Clin. Endocr. Metab. 88: 748-754, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574209</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574209" 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/10.1210/jc.2002-020830" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
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<a id="Marsh2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Marsh, D. J., Theodosopoulos, G., Martin-Schulte, K., Richardson, A.-L., Philips, J., Roher, H.-D., Delbridge, L., Robinson, B. G.
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<strong>Genome-wide copy number imbalances identified in familial and sporadic medullary thyroid carcinoma.</strong>
|
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J. Clin. Endocr. Metab. 88: 1866-1872, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12679485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12679485</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12679485" 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/10.1210/jc.2002-021155" target="_blank">Full Text</a>]
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<a id="14" class="mim-anchor"></a>
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<a id="Narod1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Narod, S. A., Sobol, H., Nakamura, Y., Calmettes, C., Baulieu, J.-L., Bigorgne, J.-C., Chabrier, G., Couette, J., de Gennes, J. L., Duprey, J., Gardet, P., Guillausseau, P.-J., Guilloteau, D., Houdent, C., Lefebvre, J., Modigliani, E., Parmentier, C., Pugeat, M., Siame, C., Tourniaire, J., Vandroux, J.-C., Vinot, J.-M., Lenoir, G. M.
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<strong>Linkage analysis of hereditary thyroid carcinoma with and without pheochromocytoma.</strong>
|
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Hum. Genet. 83: 353-358, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2572534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2572534</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2572534" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF00291380" target="_blank">Full Text</a>]
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Rakover1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Rakover, Y., Dharan, M., Luboshitsky, R.
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<strong>Hirschsprung's disease associated with isolated familial medullary carcinoma of the thyroid.</strong>
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J. Pediat. Endocr. 7: 373-377, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7735379/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7735379</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7735379" 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/10.1515/jpem.1994.7.4.373" target="_blank">Full Text</a>]
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<a id="16" class="mim-anchor"></a>
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<a id="Simpson1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Simpson, N. E.
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<strong>Personal Communication.</strong>
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Kingston, Ontario, Canada 9/3/1991.
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</ol>
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<div>
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<br />
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</div>
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </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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Cassandra L. Kniffin - updated : 5/2/2006
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</span>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 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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John A. Phillips, III - updated : 2/4/2004<br>Victor A. McKusick - updated : 11/14/2003<br>John A. Phillips, III - updated : 9/10/2003<br>John A. Phillips, III - updated : 6/6/2000
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</span>
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Creation Date:
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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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Victor A. McKusick : 5/5/1989
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </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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carol : 02/23/2024
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<span class="mim-text-font">
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ckniffin : 04/09/2014<br>terry : 5/25/2012<br>alopez : 11/22/2010<br>wwang : 2/12/2007<br>wwang : 5/4/2006<br>ckniffin : 5/2/2006<br>alopez : 2/4/2004<br>alopez : 11/17/2003<br>terry : 11/14/2003<br>alopez : 9/10/2003<br>alopez : 1/8/2003<br>alopez : 6/6/2000<br>terry : 7/24/1996<br>carol : 7/5/1996<br>terry : 7/3/1996<br>carol : 7/1/1996<br>mark : 2/9/1996<br>terry : 1/30/1996<br>terry : 1/30/1996<br>mimadm : 11/6/1994<br>davew : 8/16/1994<br>terry : 5/12/1994<br>warfield : 4/12/1994<br>supermim : 3/16/1992<br>carol : 2/22/1992
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<span class="mim-font">
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<strong>#</strong> 155240
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<h3>
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<span class="mim-font">
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THYROID CARCINOMA, FAMILIAL MEDULLARY; MTC
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
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FMTC<br />
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MTC1
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<strong>ORPHA:</strong> 653, 99361;
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<strong>DO:</strong> 0050547;
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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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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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10q11.21
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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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Medullary thyroid carcinoma
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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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155240
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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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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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RET
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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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164761
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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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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that familial MTC occurs from mutation in the RET gene (164761) on chromosome 10. Familial MTC can also be caused by mutations in the NTRK1 gene (191315) located on 1q21-q22.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Medullary thyroid carcinoma (MTC) is a malignant tumor of the calcitonin (114130)-secreting parafollicular C cells of the thyroid, and occurs sporadically or as a component of the multiple endocrine neoplasia (MEN) type 2 (see 171400)/familial medullary thyroid carcinoma (FMTC) syndromes (summary by Abu-Amero et al., 2006). Thyroid cancer derived from follicular epithelial cells is referred to as nonmedullary thyroid cancer and comprises several subtypes; see 188550. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>About 75% of medullary thyroid carcinoma is sporadic; these cases are unilateral. Bilateral multifocal medullary carcinoma is a cardinal feature of autosomal dominant multiple endocrine neoplasia type II (MEN2A; 171400). In addition, there are cases of familial medullary thyroid carcinoma in which there are no extrathyroid manifestations of multiple endocrine neoplasia; otherwise the behavior of the tumor is the same as that in the hereditary disease. Such families were observed by Farndon et al. (1986). </p><p>Primary localized cutaneous amyloidosis (PLCA), which has been observed with MEN2A, was reported also in a family in which multiple affected members had an association only with medullary thyroid carcinoma (Ferrer et al., 1991). </p><p>Rakover et al. (1994) described 2 sibs in whom isolated familial medullary carcinoma of the thyroid was diagnosed at the ages of 16 and 19 years. Hirschsprung disease was identified at the age of 1 year in both of them. Twelve other members of the family had medullary carcinoma of the thyroid. The authors stated that, although this was the first report of an association between Hirschsprung disease and isolated familial medullary carcinoma of the thyroid, the association should not be surprising because of the known association of both with mutations in the RET gene (164761). </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>Other Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Lore et al. (2000, 2001) described a 4-generation family with medullary thyroid carcinoma associated with a heterozygous RET mutation (C620S; 164761.0041). One of these individuals was found to have absence of the left kidney. Her son was found to have Hirschsprung disease (142623) at a few months of age and had undergone surgical resection of the involved intestinal segment. Subsequently, he was found to have the RET mutation and at the age of 15 years underwent total thyroidectomy, which revealed medullary thyroid carcinoma. Abnormal ultrasonography revealed the absence of the left kidney in the son also. No renal abnormalities were found on abdominal ultrasonography of the other living members. Lore et al. (2001) concluded that MEN2 syndromes may be associated with renal malformations. </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>Biochemical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By RT-PCR, Maio et al. (2003) examined the expression of a number of genes encoding cancer/testis antigens (CTAs) in 23 surgical samples of sporadic MTC. Of 11 cDNA antigens examined, NYESO1 (300156) cDNA was the most frequent, being detected in 15 of 23 examined samples (65.2%). NYESO1 expression in primary MTC tissues significantly correlated with tumor recurrence. The presence of specific anti-NYESO1 antibodies was searched in the sera of MTC-affected patients examined by ELISA using recombinant NYESO1 protein. A humoral response against this CTA was detected in 6 of 11 NYESO1-expressing patients (54.5%), and in 1 of 6 patients with an NYESO1-negative tumor. Anti-NYESO1 antibodies were present in 15 of 42 sera (35.7%), demonstrating that MTC is a neoplasm frequently associated with humoral immune response to NYESO1. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Management</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Machens et al. (2003) conducted a European multicenter study in which patients who had a RET point mutation in the germline were 20 years of age or younger, were asymptomatic, and had undergone total thyroidectomy after confirmation of the RET mutation. Altogether, 207 patients from 145 families were identified. There was a significant age-related progression from C cell hyperplasia to medullary thyroid carcinoma and, ultimately, lymph node metastasis in patients whose RET mutations were grouped according to the extracellular- and intracellular-domain codons affected and in those with mutations at codon 634 (e.g., 164761.0003). No lymph node metastases were noted in patients younger than 14 years. The age-related penetrance was unaffected by the type of amino acid substitution encoded by the various codon 634 mutations. The codon-specific differences in the age at presentation of cancer and the familial rates of concomitant adrenal and parathyroid involvement suggested that the risk of progression was based on the transforming potential of the individual RET mutations. These data provided initial guidelines for the timing of prophylactic thyroidectomy in asymptomatic carriers of RET gene mutations. </p><p>Cote and Gagel (2003) provided an optimistic review of the management of familial medullary thyroid carcinoma. They diagrammed the extracellular, transmembrane, and intracellular portions of the RET gene and presented a graph of the earliest reported age at onset of MTC according to the specific mutated RET codon. </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>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>The linkage studies of Narod et al. (1989) appear to indicate conclusively that familial medullary carcinoma of the thyroid (without pheochromocytoma) is caused by an allele in the same gene that is the site of the mutation in MEN2. They studied 18 families, 9 with MEN2 and 9 with medullary carcinoma of the thyroid without pheochromocytoma, with probes specific for the pericentromeric region of chromosome 10 and found close linkage in both cases. Genetic heterogeneity of the susceptibility locus was not observed. The genetic mutation for medullary carcinoma was in disequilibrium with alleles of 2 closely linked marker loci. </p><p>In 2 large families with medullary thyroid carcinoma (MTC1), Lairmore et al. (1991) showed that the maximum lod score between the neoplasia and marker D10Z1 was 5.88 with 0% recombination. They found no evidence for genetic heterogeneity among families with medullary thyroid carcinoma, MEN2B (162300), or MEN2A. The mutations causing these disorders thus appear to be related to each other as alleles. On the other hand, Carson et al. (1991) reported 2 families in which the MTC mutation appeared not to be linked to the pericentromeric markers on chromosome 10. </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>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>Gimm et al. (1999) used SSCP analysis of 16 exons of NTRK1 (191315) from 31 sporadic MTCs and observed variants in 5 exons (exons 4 and 14-17). Sequence analysis demonstrated 1 sequence variant each in exons 4, 14, 16, and 17, and 4 different variants in exon 15. Differential restriction enzyme digestion specific for each variant confirmed the sequencing results. All variants were also present in the corresponding germline DNA. Interestingly, the sequence variants at codon 604 (C1810T; 191315.0008) and codon 613 (G1838T; 191315.0009) of exon 15 always occurred together, possibly representing linkage disequilibrium. The frequencies of the sequence variants in germline DNA from patients with sporadic MTC did not differ significantly from those in a race-matched control group. </p><p>Marsh et al. (2003) identified chromosomal imbalances that occur in MTC including deletions of chromosomes 1p, 3q26.3-q27, 4, 9q13-q22, 13q, and 22q and amplifications of chromosome 19. These regions house known tumor suppressor genes as well as genes encoding subunits of the multicomponent complex of glycosylphosphatidylinositol-linked proteins (glial cell line-derived neurotrophic factor family receptors alpha-2-4; see 601496) and their ligands glial cell line-derived neurotrophic factor (600837), neurturin (602018), persephin (602921), and artemin (603886) that facilitate RET dimerization and downstream signaling. Chromosomal imbalances in the MTC cell line TT were largely identical to those identified in primary MTC tumors, consolidating its use as a model for studying MTC. </p><p>Abu-Amero et al. (2006) identified nonsynonymous germline mitochondrial DNA (mtDNA) mutations in both normal and tumor tissue from 20 (76.9%) of 26 cases of medullary thyroid carcinoma, including 9 (69.2%) of 13 sporadic cases and 11 (84.6%) of 13 familial cases; 10 of 13 familial cases were patients with MEN2. The familial cases tended to have transversion mtDNA mutations rather than transition mutations. All 13 familial cases also had germline RET mutations. Abu-Amero et al. (2006) suggested that mtDNA mutations may be involved in medullary thyroid carcinoma tumorigenesis and/or progression. </p><p><strong><em>Reclassified Variants</em></strong></p><p>
|
|
The Y791F variant (164761.0034) in the RET gene that was identified in patients with familial medullary thyroid carcinoma by Baumgartner-Parzer et al. (2005) has been reclassified as a variant of unknown significance. </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>Simpson (1991) proposed a branching classification of the forms of medullary thyroid carcinoma (MTC). MTC has 2 forms: MTC1 (with no other primary tumors) and MEN2. MEN2 has 2 forms: MEN2A and MEN2B. MEN2A has 3 forms: MEN2A-1 (MTC with pheochromocytoma and parathyroid tumor), MEN2A-2 (MTC with pheochromocytoma), and MEN2A-3 (MTC with parathyroid tumor).</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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<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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Abu-Amero, K. K., Alzahrani, A. S., Zou, M., Shi, Y.
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<strong>Association of mitochondrial DNA transversion mutations with familial medullary thyroid carcinoma/multiple endocrine neoplasia type 2 syndrome.</strong>
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Oncogene 25: 677-684, 2006.
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[PubMed: 16205644]
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[Full Text: https://doi.org/10.1038/sj.onc.1209094]
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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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Baumgartner-Parzer, S. M., Lang, R., Wagner, L., Heinze, G., Niederle, B., Kaserer, K., Waldhausl, W., Vierhapper, H.
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<strong>Polymorphisms in exon 13 and intron 14 of the RET protooncogene: genetic modifiers of medullary thyroid carcinoma?</strong>
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J. Clin. Endocr. Metab. 90: 6232-6236, 2005.
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[PubMed: 16118333]
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[Full Text: https://doi.org/10.1210/jc.2005-1278]
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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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Carson, N. L., Simpson, N. E., Myers, S., Anderson, L., Clarke, C., Simpson, W. J., Bridge, P. J.
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<strong>Genetic heterogeneity in families with familial medullary thyroid carcinoma. (Abstract)</strong>
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Cytogenet. Cell Genet. 58: 1948 only, 1991.
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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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Cote, G. J., Gagel, R. F.
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<strong>Lessons learned from the management of a rare genetic cancer. (Editorial)</strong>
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New Eng. J. Med. 349: 1566-1568, 2003.
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[PubMed: 14561800]
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[Full Text: https://doi.org/10.1056/NEJMe038148]
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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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Farndon, J. R., Leight, G. S., Dilley, W. G., Baylin, S. B., Smallridge, R. C., Harrison, T. S., Wells, S. A., Jr.
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<strong>Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity.</strong>
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Brit. J. Surg. 73: 278-281, 1986.
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[PubMed: 3697657]
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[Full Text: https://doi.org/10.1002/bjs.1800730411]
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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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Ferrer, J. P., Halperin, I., Conget, J. I., Alsina, M., Martinez-Osaba, M. J., Palou, J., Bombi, J. A., Vilardell, E.
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<strong>Primary localized cutaneous amyloidosis and familial medullary thyroid carcinoma.</strong>
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Clin. Endocr. 34: 435-439, 1991.
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[PubMed: 1889128]
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[Full Text: https://doi.org/10.1111/j.1365-2265.1991.tb00322.x]
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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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Gimm, O., Greco, A., Hoang-Vu, C., Dralle, H., Pierotti, M. A., Eng, C.
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<strong>Mutation analysis reveals novel sequence variants in NTRK1 in sporadic human medullary thyroid carcinoma.</strong>
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J. Clin. Endocr. Metab. 84: 2784-2787, 1999.
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[PubMed: 10443680]
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[Full Text: https://doi.org/10.1210/jcem.84.8.5901]
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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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Lairmore, T. C., Howe, J. R., Korte, J. A., Dilley, W. G., Aine, L., Aine, E., Wells, S. A., Jr., Donis-Keller, H.
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<strong>Familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2B map to the same region of chromosome 10 as multiple endocrine neoplasia type 2A.</strong>
|
|
Genomics 9: 181-192, 1991. Note: Erratum: Genomics 10: 514 only, 1991.
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[PubMed: 1672289]
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[Full Text: https://doi.org/10.1016/0888-7543(91)90237-9]
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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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Lore, F., Di Cairano, G., Talidis, F.
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<strong>Unilateral renal agenesis in a family with medullary thyroid carcinoma. (Letter)</strong>
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New Eng. J. Med. 342: 1218-1219, 2000.
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[PubMed: 10777380]
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[Full Text: https://doi.org/10.1056/NEJM200004203421615]
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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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Lore, F., Talidis, F., Di Cairano, G., Renieri, A.
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<strong>Multiple endocrine neoplasia type 2 syndromes may be associated with renal malformations.</strong>
|
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J. Intern. Med. 250: 37-42, 2001.
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[PubMed: 11454140]
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[Full Text: https://doi.org/10.1046/j.1365-2796.2001.00846.x]
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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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Machens, A., Niccoli-Sire, P., Hoegel, J., Frank-Raue, K., van Vroonhoven, T. J., Roeher, H.-D., Wahl, R. A., Lamesch, P., Raue, F., Conte-Devolx, B., Dralle, H.
|
|
<strong>Early malignant progression of hereditary medullary thyroid cancer.</strong>
|
|
New Eng. J. Med. 349: 1517-1525, 2003.
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[PubMed: 14561794]
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[Full Text: https://doi.org/10.1056/NEJMoa012915]
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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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Maio, M., Coral, S., Sigalotti, L., Elisei, R., Romei, C., Rossi, G., Cortini, E., Colizzi, F., Fenzi, G., Altomonte, M., Pinchera, A., Vitale, M.
|
|
<strong>Analysis of cancer/testis antigens in sporadic medullary thyroid carcinoma: expression and humoral response to NY-ESO-1.</strong>
|
|
J. Clin. Endocr. Metab. 88: 748-754, 2003.
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[PubMed: 12574209]
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[Full Text: https://doi.org/10.1210/jc.2002-020830]
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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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Marsh, D. J., Theodosopoulos, G., Martin-Schulte, K., Richardson, A.-L., Philips, J., Roher, H.-D., Delbridge, L., Robinson, B. G.
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<strong>Genome-wide copy number imbalances identified in familial and sporadic medullary thyroid carcinoma.</strong>
|
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J. Clin. Endocr. Metab. 88: 1866-1872, 2003.
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[PubMed: 12679485]
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[Full Text: https://doi.org/10.1210/jc.2002-021155]
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Narod, S. A., Sobol, H., Nakamura, Y., Calmettes, C., Baulieu, J.-L., Bigorgne, J.-C., Chabrier, G., Couette, J., de Gennes, J. L., Duprey, J., Gardet, P., Guillausseau, P.-J., Guilloteau, D., Houdent, C., Lefebvre, J., Modigliani, E., Parmentier, C., Pugeat, M., Siame, C., Tourniaire, J., Vandroux, J.-C., Vinot, J.-M., Lenoir, G. M.
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<strong>Linkage analysis of hereditary thyroid carcinoma with and without pheochromocytoma.</strong>
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Hum. Genet. 83: 353-358, 1989.
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[PubMed: 2572534]
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[Full Text: https://doi.org/10.1007/BF00291380]
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<p class="mim-text-font">
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Rakover, Y., Dharan, M., Luboshitsky, R.
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<strong>Hirschsprung's disease associated with isolated familial medullary carcinoma of the thyroid.</strong>
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J. Pediat. Endocr. 7: 373-377, 1994.
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[PubMed: 7735379]
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[Full Text: https://doi.org/10.1515/jpem.1994.7.4.373]
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Simpson, N. E.
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<strong>Personal Communication.</strong>
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Kingston, Ontario, Canada 9/3/1991.
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Cassandra L. Kniffin - updated : 5/2/2006<br>John A. Phillips, III - updated : 2/4/2004<br>Victor A. McKusick - updated : 11/14/2003<br>John A. Phillips, III - updated : 9/10/2003<br>John A. Phillips, III - updated : 6/6/2000
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Victor A. McKusick : 5/5/1989
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