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- *600618 - ETS VARIANT TRANSCRIPTION FACTOR 6; ETV6
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*600618</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cytogenetics">Cytogenetics</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#history">History</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/600618">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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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 id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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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="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000139083;t=ENST00000396373" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=2120" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=600618" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</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="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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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="mimDnaLinksFold" 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.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000139083;t=ENST00000396373" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001413913,NM_001413914,NM_001413915,NM_001413916,NM_001413917,NM_001413918,NM_001987,XM_011520612,XM_017018990,XM_017018991,XM_047428502,XM_047428503,XM_047428504" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_001987" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=600618" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</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="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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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="mimProteinLinksFold" 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://hprd.org/summary?hprd_id=15976&isoform_id=15976_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/ETV6" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/511283,601904,730927,1181839,1532159,1621109,1621111,1764088,1764142,4503611,27695076,90968068,119616646,158259905,767971806,957949344,957949347,1034578523,1034578525,1421616448,2217288020,2217288024,2217288026,2327747142,2327747169,2327747171,2327747201,2327747224,2327747252" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P41212" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</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="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" 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="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</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="mimGeneInfoLinksFold" 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="http://biogps.org/#goto=genereport&id=2120" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000139083;t=ENST00000396373" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=ETV6" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=ETV6" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+2120" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/ETV6" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:2120" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/2120" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr12&hgg_gene=ENST00000396373.9&hgg_start=11649674&hgg_end=11895377&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</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="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="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="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse 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://search.clinicalgenome.org/kb/gene-dosage/HGNC:3495" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:3495" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=600618[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>
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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="mimVariation">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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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="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=600618[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000139083" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=ETV6" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=ETV6" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ETV6" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=ETV6&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA27909" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</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/gene/HGNC:3495" 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="https://flybase.org/reports/FBgn0000097.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:109336" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/ETV6#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:109336" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/2120/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=2120" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00016865;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00016865 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00304788;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00304788 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-010727-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</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="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</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="mimCellularPathwaysLinksFold" 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.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2120" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=ETV6&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
|
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
|
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
600618
|
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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>
|
|
<span class="mim-font">
|
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|
ETS VARIANT TRANSCRIPTION FACTOR 6; ETV6
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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>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
|
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<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
ETS VARIANT GENE 6<br />
|
|
TRANSLOCATION, ETS, LEUKEMIA; TEL<br />
|
|
TEL1 ONCOGENE
|
|
</span>
|
|
</h4>
|
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</div>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="includedTitles" class="mim-anchor"></a>
|
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<div>
|
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<p>
|
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<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
|
<span class="h3 mim-font">
|
|
ETV6/PDGFRB FUSION GENE, INCLUDED
|
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</span>
|
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</div>
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<div>
|
|
<span class="h4 mim-font">
|
|
|
|
ETV6/MN1 FUSION GENE, INCLUDED<br />
|
|
ETV6/AML1 FUSION GENE, INCLUDED<br />
|
|
ETV6/ARNT FUSION GENE, INCLUDED<br />
|
|
ETV6/MDS2 FUSION GENE, INCLUDED<br />
|
|
ETV6/ABL2 FUSION GENE, INCLUDED<br />
|
|
ETV6/PER1 FUSION GENE, INCLUDED<br />
|
|
ETV6/NTRK3 FUSION GENE, INCLUDED<br />
|
|
ETV6/ACS2 FUSION GENE, INCLUDED<br />
|
|
ETV6/BTL FUSION GENE, INCLUDED<br />
|
|
ETV6/JAK2 FUSION GENE, INCLUDED<br />
|
|
ETV6/RUNX1 FUSION GENE, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=ETV6" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">ETV6</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/12/174?start=-3&limit=10&highlight=174">12p13.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr12:11649674-11895377&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">12:11,649,674-11,895,377</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=601626,616216" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
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|
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<p>The ETV6 gene encodes an ETS family transcriptional repressor and is frequently rearranged or fused with other genes in human leukemias of myeloid or lymphoid origins (<a href="#34" class="mim-tip-reference" title="Wang, L. C., Kuo, F., Fujiwara, Y., Gilliland, D. G., Golub, T. R., Orkin, S. H. <strong>Yolk sac angiogenic defect and intra-embryonic apoptosis in mice lacking the Ets-related factor TEL.</strong> EMBO J. 16: 4374-4383, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9250681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9250681</a>] [<a href="https://doi.org/10.1093/emboj/16.14.4374" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9250681">Wang et al., 1997</a>; summary by <a href="#37" class="mim-tip-reference" title="Zhang, M. Y., Churpek, J. E., Keel, S. B., Walsh, T., Lee, M. K., Loeb, K. R., Gulsuner, S., Pritchard, C. C., Sanchez-Bonilla, M., Delrow, J. L., Basom, R. S., Forouhar, M., and 14 others. <strong>Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.</strong> Nature Genet. 47: 180-185, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25581430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25581430</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25581430[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25581430">Zhang et al., 2015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9250681+25581430" 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="#13" class="mim-tip-reference" title="Golub, T. R., Barker, G. F., Lovett, M., Gilliland, D. G. <strong>Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation.</strong> Cell 77: 307-316, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8168137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8168137</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90322-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8168137">Golub et al. (1994)</a> identified the ETV6 gene as part of a fusion transcript resulting from a somatic t(5;12)(q33;p13) translocation in chronic myelomonocytic leukemia (see <a href="/entry/607785">607785</a>) cancer cells. The translocation was found to consist of a novel gene on chromosome 12p13 and the PDGFRB (<a href="/entry/173410">173410</a>) gene on 5q33. <a href="#13" class="mim-tip-reference" title="Golub, T. R., Barker, G. F., Lovett, M., Gilliland, D. G. <strong>Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation.</strong> Cell 77: 307-316, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8168137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8168137</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90322-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8168137">Golub et al. (1994)</a> isolated clones corresponding to the coding sequence from a chromosome 12 cDNA library. Portions of the gene showed homology to the ETS family of transcription factors, and it was designated 'TEL' for translocation, ETS, leukemia. Northern blot analysis detected 3 transcripts of 6.5 kb, 4.5 kb, and 2.4 kb in all tissues examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8168137" 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="#3" class="mim-tip-reference" title="Baens, M., Peeters, P., Guo, C., Aerssens, J., Marynen, P. <strong>Genomic organization of TEL: the human ETS-variant gene 6.</strong> Genome Res. 6: 404-413, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8743990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8743990</a>] [<a href="https://doi.org/10.1101/gr.6.5.404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8743990">Baens et al. (1996)</a> developed contigs containing the complete coding sequence and the 5-prime and 3-prime UTRs of the ETV6 gene. The helix-loop-helix (HLH) motif is coded by exons 3 and 4, whereas exons 6 to 8 encode for the ETS DNA-binding domain. The ETV6 gene is flanked at its 5-prime and 3-prime ends by markers D12S1697 and D12S98, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8743990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#3" class="mim-tip-reference" title="Baens, M., Peeters, P., Guo, C., Aerssens, J., Marynen, P. <strong>Genomic organization of TEL: the human ETS-variant gene 6.</strong> Genome Res. 6: 404-413, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8743990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8743990</a>] [<a href="https://doi.org/10.1101/gr.6.5.404" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8743990">Baens et al. (1996)</a> determined that the ETV6 gene contains 8 exons spanning 240 kb. They identified an alternative exon 1B located within intron 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8743990" 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="#32" class="mim-tip-reference" title="Stegmaier, K., Pendse, S., Barker, G. F., Bray-Ward, P., Ward, D. C., Montgomery, K. T., Krauter, K. S., Reynolds, C., Sklar, J., Donnelly, M., Bohlander, S. K., Rowley, J. D., Sallan, S. E., Gilliland, D. G., Golub, T. R. <strong>Frequent loss of heterozygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood.</strong> Blood 86: 38-44, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795247</a>]" pmid="7795247">Stegmaier et al. (1995)</a> mapped the ETV6 gene to chromosome 12p13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7795247" 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="#32" class="mim-tip-reference" title="Stegmaier, K., Pendse, S., Barker, G. F., Bray-Ward, P., Ward, D. C., Montgomery, K. T., Krauter, K. S., Reynolds, C., Sklar, J., Donnelly, M., Bohlander, S. K., Rowley, J. D., Sallan, S. E., Gilliland, D. G., Golub, T. R. <strong>Frequent loss of heterozygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood.</strong> Blood 86: 38-44, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795247</a>]" pmid="7795247">Stegmaier et al. (1995)</a> presented evidence that the TEL gene may act as a tumor suppressor gene. They noted noted that 5% of children with acute lymphocytic leukemia (ALL) have 12p13-p12 deletions. Using markers flanking the TEL gene, <a href="#32" class="mim-tip-reference" title="Stegmaier, K., Pendse, S., Barker, G. F., Bray-Ward, P., Ward, D. C., Montgomery, K. T., Krauter, K. S., Reynolds, C., Sklar, J., Donnelly, M., Bohlander, S. K., Rowley, J. D., Sallan, S. E., Gilliland, D. G., Golub, T. R. <strong>Frequent loss of heterozygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood.</strong> Blood 86: 38-44, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795247</a>]" pmid="7795247">Stegmaier et al. (1995)</a> found that 15% of 81 informative children with ALL had TEL loss of heterozygosity that was not evident on cytogenetic analysis. Detailed examination showed that the critically deleted region included 2 candidate suppressor genes: TEL and KIP (<a href="/entry/600778">600778</a>), the gene encoding the cyclin-dependent kinase inhibitor p27. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7795247" 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>ETV6/PDGFRB Fusion Gene</em></strong></p><p>
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In bone marrow cells from a 17-year-old male with chronic myelomonocytic leukemia, <a href="#13" class="mim-tip-reference" title="Golub, T. R., Barker, G. F., Lovett, M., Gilliland, D. G. <strong>Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation.</strong> Cell 77: 307-316, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8168137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8168137</a>] [<a href="https://doi.org/10.1016/0092-8674(94)90322-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8168137">Golub et al. (1994)</a> identified a somatic t(5;12)(q33;p13) translocation consisting of the 154 N terminal residues of ETV6 linked to the transmembrane and tyrosine kinase domains of the PDGFRB on chromosome 5q33. The entire ligand-binding domain of PDGFRB and the putative DNA-binding domain of ETV6 were both excluded from the fusion transcript. This same rearrangement was detected in 3 additional patients with chronic myelomonocytic leukemia. The index patient subsequently developed acute myelogenous leukemia (AML; <a href="/entry/601626">601626</a>) associated with other genetic alterations, suggesting that the t(5;12)(q33;p13) translocation was an early step in a multistep progression to full AML. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8168137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Apperley, J. F., Gardembas, M., Melo, J. V., Russell-Jones, R., Bain, B. J., Baxter, E. J., Chase, A., Chessells, J. M., Colombat, M., Dearden, C. E., Dimitrijevic, S., Mahon, F.-X., Marin, D., Nikolova, Z., Olavarria, E., Silberman, S., Schultheis, B., Cross, N. C. P., Goldman, J. M. <strong>Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta.</strong> New Eng. J. Med. 347: 481-487, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12181402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12181402</a>] [<a href="https://doi.org/10.1056/NEJMoa020150" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12181402">Apperley et al. (2002)</a> reported successful response to therapy with the tyrosine kinase inhibitor imatinib mesylate in 3 patients with chronic myeloproliferative disorder (<a href="/entry/131440">131440</a>) and a t(5;12) translocation. The patients' leukemic cells carried the ETV6/PDGFRB fusion gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12181402" 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="#27" class="mim-tip-reference" title="Pierce, A., Carney, L., Hamza, H. G., Griffiths, J. R., Zhang, L., Whetton, B. A., Gonzalez Sanchez, M. B., Tamura, T., Sternberg, D., Whetton, A. D. <strong>THOC5 spliceosome protein: a target for leukaemogenic tyrosine kinases that affects inositol lipid turnover.</strong> Brit. J. Haemat. 141: 641-650, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18373705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18373705</a>] [<a href="https://doi.org/10.1111/j.1365-2141.2008.07090.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18373705">Pierce et al. (2008)</a> showed that expression of TEL/PDGFRB in murine myeloid FDCP-Mix cells prevented cell differentiation, increased cell survival, increased the level of phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3), and increased the expression and phosphorylation of Thoc5 (<a href="/entry/612733">612733</a>). Elevated Thoc5 expression also led to increased cell survival and PtdInsP3 levels, suggesting that the effects associated with TEL/PDGFRB expression were due, at least in part, to Thoc5 upregulation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18373705" 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>ETV6/AML1 Fusion Gene</em></strong></p><p>
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<a href="#12" class="mim-tip-reference" title="Golub, T. R., Barker, G. F., Bohlander, S. K., Hiebert, S. W., Ward, D. C., Bray-Ward, P., Morgan, E., Raimondi, S. C., Rowley, J. D., Gilliland, D. G. <strong>Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia.</strong> Proc. Nat. Acad. Sci. 92: 4917-4921, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7761424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7761424</a>] [<a href="https://doi.org/10.1073/pnas.92.11.4917" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7761424">Golub et al. (1995)</a> documented fusion of TEL to the AML1 gene (<a href="/entry/151385">151385</a>) on chromosome 21 in 2 pediatric patients with acute lymphocytic leukemia with t(12;21) translocations. The findings implicated TEL in the pathogenesis of leukemia through its fusion to either a receptor tyrosine kinase, such as PDGFRB, or a transcription factor, such as AML1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7761424" 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>Using RT-PCR, <a href="#29" class="mim-tip-reference" title="Romana, S. P., Poirel, H., Leconiat, M., Flexor, M.-A., Mauchauffe, M., Jonveaux, P., Macintyre, E. A., Berger, R., Bernard, O. A. <strong>High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia.</strong> Blood 86: 4263-4269, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7492786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7492786</a>]" pmid="7492786">Romana et al. (1995)</a> identified the TEL/AML1 fusion gene in 8 (16%) of 46 childhood B-cell lymphoblastic leukemia cells, only 1 of which showed a 12p abnormality by classic cytogenetic techniques. The authors concluded that t(12;21) is the most frequent translocation in childhood B-lineage ALL. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7492786" 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="#11" class="mim-tip-reference" title="Ford, A. M., Bennett, C. A., Price, C. M., Bruin, M. C. A., Van Wering, E. R., Greaves, M. <strong>Fetal origins of the TEL-AML1 fusion gene in identical twins with leukemia.</strong> Proc. Nat. Acad. Sci. 95: 4584-4588, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9539781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9539781</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9539781[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.95.8.4584" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9539781">Ford et al. (1998)</a> reported the extraordinary case of monozygotic twins in whom common acute lymphoblastic leukemia was diagnosed at ages 3.5 years and 4 years. The twins' leukemic DNA shared the same unique (or clonotypic) but nonconstitutive TEL/AML1 fusion sequence. The most plausible explanation for this finding was thought to be a single cell origin of the TEL/AML fusion in 1 fetus in utero, probably as a leukemia-initiating mutation, followed by intraplacental metastasis of clonal progeny to the other twin. Clonal identity was further supported by the finding that the leukemic cells in the twins shared an identical rearranged IGH allele. These data had implications for the etiology and natural history of childhood leukemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9539781" 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>ETV6/MN1 Fusion Gene</em></strong></p><p>
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<a href="#7" class="mim-tip-reference" title="Buijs, A., Sherr, S., van Baal, S., van Bezouw, S., van der Plas, D., Geurts van Kessel, A., Riegman, P., Lekanne Deprez, R., Zwarthoff, E., Hagemeijer, A., Grosveld, G. <strong>Translocation (12;22)(p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12q13 to the MN1 gene on 22q11.</strong> Oncogene 10: 1511-1519, 1995. Note: Erratum: Oncogene 11: 809 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7731705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7731705</a>]" pmid="7731705">Buijs et al. (1995)</a> showed that the MN1 gene (<a href="/entry/156100">156100</a>) on 22q11 is fused to the TEL gene in the t(12;22)(p13;q11) translocation that is observed in different myeloid malignancies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7731705" 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>ETV6/JAK2 Fusion Gene</em></strong></p><p>
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<a href="#25" class="mim-tip-reference" title="Peeters, P., Raynaud, S. D., Cools, J., Wlodarska, I., Grosgeorge, J., Philip, P., Monpoux, F., Van Rompaey, L., Baens, M., Van den Berghe, H., Marynen, P. <strong>Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia.</strong> Blood 90: 2535-2540, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326218</a>]" pmid="9326218">Peeters et al. (1997)</a> identified a t(9;12)(p24;p13) translocation in a patient with early pre-B acute lymphoid leukemia and a t(9;15;12)(p24;q15;p13) translocation in a patient with atypical chronic myelogenous leukemia (CML; <a href="/entry/608232">608232</a>) in transformation. Both changes involved the ETV6 gene at 12p13 and the JAK2 gene (<a href="/entry/147796">147796</a>) at 9p24. In each case different fusion mRNAs were found, with only 1 resulting in a chimeric protein consisting of the oligomerization domain of ETV6 and the protein tyrosine kinase domain of JAK2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Lacronique, V., Boureux, A., Della Valle, V., Poirel, H., Quang, C. T., Mauchauffe, M., Berthou, C., Lessard, M., Berger, R., Ghysdael, J., Bernard, O. A. <strong>A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia.</strong> Science 278: 1309-1312, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9360930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9360930</a>] [<a href="https://doi.org/10.1126/science.278.5341.1309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9360930">Lacronique et al. (1997)</a> observed a t(9;12)(p24;p13) translocation in leukemic cells from a 4-year-old boy with T-cell ALL. The 3-prime portion of the JAK2 gene was fused to the 5-prime portion of the ETV6 gene, resulting in a protein containing the catalytic domain of JAK2 and the oligomerization domain of ETV6. The resultant protein had constitutive tyrosine kinase activity and conferred cytokine-independent proliferation to a murine cell line. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9360930" 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>ETV6/NTRK3 Fusion Gene</em></strong></p><p>
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<a href="#15" class="mim-tip-reference" title="Knezevich, S. R., McFadden, D. E., Tao, W., Lim, J. F., Sorensen, P. H. B. <strong>A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma.</strong> Nature Genet. 18: 184-187, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9462753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9462753</a>] [<a href="https://doi.org/10.1038/ng0298-184" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9462753">Knezevich et al. (1998)</a> detected a recurrent t(12;15)(p13;q25) translocation consisting of fusion of the ETV6 gene with the NTRK3 gene (<a href="/entry/191316">191316</a>) on 15q25 in 3 congenital fibrosarcomas analyzed. Congenital (or infantile) fibrosarcoma (CFS) is a malignant tumor of fibroblasts that occurs in patients aged 2 or younger. CFS is unique among human sarcomas in that it has an excellent prognosis and very low metastatic rate. CFS is histologically identical to adult-type fibrosarcoma (ATFS); however, ATFS is an aggressive malignancy of adults and older children that has a poor prognosis. The same translocation was not identified in ATFS or infantile fibromatosis (<a href="/entry/228550">228550</a>), a histologically similar but benign fibroblastic proliferation occurring in the same age group as CFS. ETV6/NTRK3 fusion transcripts encoded the HLH protein dimerization domain of ETV6 fused to the protein tyrosine kinase (PTK) domain of NTRK3. Presumably, the chimeric protein tyrosine kinase contributed to oncogenesis by dysregulation of NTRK3 signal transduction pathways. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9462753" 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>ETV6/ACS2 Fusion Gene</em></strong></p><p>
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<a href="#36" class="mim-tip-reference" title="Yagasaki, F., Jinnai, I., Yoshida, S., Yokoyama, Y., Matsuda, A., Kusumoto, S., Kobayashi, H., Terasaki, H., Ohyashiki, K., Asou, N., Murohashi, I., Bessho, M., Hirashima, K. <strong>Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13).</strong> Genes Chromosomes Cancer 26: 192-202, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502316</a>] [<a href="https://doi.org/10.1002/(sici)1098-2264(199911)26:3<192::aid-gcc2>3.0.co;2-e" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10502316">Yagasaki et al. (1999)</a> identified a recurrent t(5;12)(q31;p13) translocation, resulting in an ETV6/ACS2 (<a href="/entry/604443">604443</a>) fusion gene in a patient with refractory anemia with excess blasts with basophilia, a patient with AML with eosinophilia, and a patient with acute eosinophilic leukemia (AEL). The ETV6/ACS2 fusion transcripts showed an out-frame fusion of exon 1 of ETV6 to exon 1 of ACS2 in the patient with AEL, an out-frame fusion of exon 1 of ETV6 to exon 11 of ACS2 in the patient with AML, and a short in-frame fusion of exon 1 of ETV6 to the 3-prime untranslated region of ACS2 in the patient with refractory anemia. Reciprocal ACS2/ETV6 transcripts were identified in 2 of the cases. FISH with ETV6 cosmids on 12p13, and BACs and PIs on 5q31, demonstrated that the 5q31 breakpoints of the AML and AEL cases involved the 5-prime portion of the ACS2 gene, and that the 5q31 breakpoint of the refractory anemia case involved the 3-prime portion of the ACS2 gene. None of the resulting chimeric transcripts except for the ACS2/ETV6 transcript in the refractory anemia case led to a fusion protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502316" 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>ETV6/ABL2 Fusion Gene</em></strong></p><p>
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<a href="#9" class="mim-tip-reference" title="Cazzaniga, G., Tosi, S., Aloisi, A., Giudici, G., Daniotti, M., Pioltelli, P., Kearney, L., Biondi, A. <strong>The tyrosine kinase Abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts.</strong> Blood 94: 4370-4373, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10590083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10590083</a>]" pmid="10590083">Cazzaniga et al. (1999)</a> identified a t(1;12)(q25;p13) translocation involving the ETV6 gene and the ABL2 (<a href="/entry/164690">164690</a>) gene in a patient with acute myeloid leukemia M4 with eosinophilia. The novel transcript resulted in a chimeric protein consisting of the helix-loop-helix oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase domains of ABL2. The reciprocal transcript ABL2/ETV6 was also detected in the patient's RNA by RT-PCR, although at a lower expression level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10590083" 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>ETV6/BTL Fusion Gene</em></strong></p><p>
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<a href="#10" class="mim-tip-reference" title="Cools, J., Bilhou-Nabera, C., Wlodarska, I., Cabrol, C., Talmant, P., Bernard, P., Hagemeijer, A., Marynen, P. <strong>Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13).</strong> Blood 94: 1820-1824, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10477709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10477709</a>]" pmid="10477709">Cools et al. (1999)</a> reported 4 cases of acute myeloid leukemia with very immature myeloblasts and a t(4;12)(q11-q12;p13) translocation in which ETV6 was linked with the BTL gene (<a href="/entry/604332">604332</a>). RT-PCR experiments indicated that expression of the BTL/ETV6 transcript, but not of the reciprocal ETV6/BTL transcript, was a common finding in these leukemias. In contrast to most of the other ETV6 fusions, both the complete helix-loop-helix and ETS DNA-binding domains of ETV6 were present in the predicted BTL/ETV6 fusion protein, and a chimeric gene was transcribed from the BTL promoter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10477709" 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>ETV6/ARNT Fusion Gene</em></strong></p><p>
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<a href="#30" class="mim-tip-reference" title="Salomon-Nguyen, F., Della-Valle, V., Mauchauffe, M., Busson-Le Coniat, M., Ghysdael, J., Berger, R., Bernard, O. A. <strong>The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion.</strong> Proc. Nat. Acad. Sci. 97: 6757-6762, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10829078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10829078</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10829078[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.120162297" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10829078">Salomon-Nguyen et al. (2000)</a> determined that a t(1;12)(q21;p13) translocation observed in a case of acute myeloblastic leukemia (AML-M2) resulted in a fusion protein containing the amino-terminal of TEL and essentially all of the ARNT gene (<a href="/entry/126110">126110</a>). The involvement of ARNT in human leukemogenesis had not previously been described. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10829078" 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>ETV6/MDS2 Fusion Gene</em></strong></p><p>
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<a href="#22" class="mim-tip-reference" title="Odero, M. D., Vizmanos, J. L., Roman, J. P., Lahortiga, I., Panizo, C., Calasanz, M. J., Zeleznik-Le, N. J., Rowley, J. D., Novo, F. J. <strong>A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a patient with myelodysplastic syndrome.</strong> Genes Chromosomes Cancer 35: 11-19, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12203785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12203785</a>] [<a href="https://doi.org/10.1002/gcc.10090" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12203785">Odero et al. (2002)</a> identified a t(1;12)(p36.1;p13) translocation in an MDS patient that resulted in the fusion of exons 1 and 2 of ETV6 to exons 6 and 7 of MDS2 (<a href="/entry/607305">607305</a>). The predicted protein is out of frame and contains the first 54 amino acids of ETV6 followed by 4 novel amino acids from the MDS2 sequence. The truncated ETV6 protein lacks critical functional domains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12203785" 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>ETV6/PER1 Fusion Gene</em></strong></p><p>
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<a href="#26" class="mim-tip-reference" title="Penas, E. M. M., Cools, J., Algenstaedt, P., Hinz, K., Seeger, D., Schafhausen, P., Schilling, G., Marynen, P., Hossfeld, D. K., Dierlamm, J. <strong>A novel cryptic translocation t(12;17)(p13;p12-p13) in a secondary acute myeloid leukemia results in a fusion of the ETV6 gene and the antisense strand of the PER1 gene.</strong> Genes Chromosomes Cancer 37: 79-83, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12661008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12661008</a>] [<a href="https://doi.org/10.1002/gcc.10175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12661008">Penas et al. (2003)</a> cloned a novel cryptic translocation, t(12;17)(p13;p12-p13), occurring in a patient with acute myeloid leukemia evolving from a chronic myelomonocytic leukemia. They identified a fusion transcript between exon 1 of the ETV6 gene and the antisense strand of PER1 (<a href="/entry/602260">602260</a>). The ETV6/PER1 fusion transcript did not produce a fusion protein, and no other fusion transcripts could be detected. <a href="#26" class="mim-tip-reference" title="Penas, E. M. M., Cools, J., Algenstaedt, P., Hinz, K., Seeger, D., Schafhausen, P., Schilling, G., Marynen, P., Hossfeld, D. K., Dierlamm, J. <strong>A novel cryptic translocation t(12;17)(p13;p12-p13) in a secondary acute myeloid leukemia results in a fusion of the ETV6 gene and the antisense strand of the PER1 gene.</strong> Genes Chromosomes Cancer 37: 79-83, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12661008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12661008</a>] [<a href="https://doi.org/10.1002/gcc.10175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12661008">Penas et al. (2003)</a> hypothesized that in the absence of a fusion protein, the inactivation of PER1 or deregulation of a gene in the neighborhood of PER1 may contribute to the pathogenesis of leukemia with this translocation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12661008" 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>ETV6/RUNX1 Fusion Gene</em></strong></p><p>
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<a href="#1" class="mim-tip-reference" title="Anderson, K., Lutz, C., van Delft, F. W., Bateman, C. M., Guo, Y., Colman, S. M., Kempski, H., Moorman, A. V., Titley, I., Swansbury, J., Kearney, L., Enver, T., Greaves, M. <strong>Genetic variegation of clonal architecture and propagating cells in leukaemia.</strong> Nature 469: 356-361, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21160474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21160474</a>] [<a href="https://doi.org/10.1038/nature09650" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21160474">Anderson et al. (2011)</a> examined the genetic architecture of cancer at the subclonal and single-cell level and in cells responsible for cancer clone maintenance and propagation in childhood acute lymphoblastic leukemia (ALL; see <a href="/entry/613065">613065</a>) in which the ETV6/RUNX1 (<a href="/entry/151385">151385</a>) gene fusion is an early or initiating genetic lesion followed by a modest number of recurrent or driver copy number alterations. By multiplexing fluorescence in situ hybridization probes for these mutations, up to 8 genetic abnormalities could be detected in single cells, a genetic signature of subclones identified, and a composite picture of subclonal architecture and putative ancestral trees assembled. <a href="#1" class="mim-tip-reference" title="Anderson, K., Lutz, C., van Delft, F. W., Bateman, C. M., Guo, Y., Colman, S. M., Kempski, H., Moorman, A. V., Titley, I., Swansbury, J., Kearney, L., Enver, T., Greaves, M. <strong>Genetic variegation of clonal architecture and propagating cells in leukaemia.</strong> Nature 469: 356-361, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21160474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21160474</a>] [<a href="https://doi.org/10.1038/nature09650" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21160474">Anderson et al. (2011)</a> observed that subclones in acute lymphoblastic leukemia have variegated genetics and complex nonlinear or branching evolutionary histories. Copy number alterations are independently and reiteratively acquired in subclones of individual patients, and in no preferential order. Clonal architecture is dynamic and is subject to change in the lead-up to a diagnosis and in relapse. Leukemia-propagating cells, assayed by serial transplantation in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) IL2R-gamma (<a href="/entry/308380">308380</a>)-null mice, are also genetically variegated, mirroring subclonal patterns, and vary in competitive regenerative capacity in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21160474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The ETV6/RUNX1 fusion gene, found in 25% of childhood ALL cases, is acquired in utero but requires additional somatic mutations for overt leukemia. <a href="#24" class="mim-tip-reference" title="Papaemmanuil, E., Rapado, I., Li, Y., Potter, N. E., Wedge, D. C., Tubio, J., Alexandrov, L. B., Van Loo, P., Cooke, S. L., Marshall, J., Martincorena, I., Hinton, J., and 25 others. <strong>RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia.</strong> Nature Genet. 46: 116-125, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24413735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24413735</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24413735[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24413735">Papaemmanuil et al. (2014)</a> used exome and low-coverage whole-genome sequencing to characterize secondary events associated with leukemic transformation. RAG (see <a href="/entry/179615">179615</a>)-mediated deletions emerged as the dominant mutational process, characterized by recombination signal sequence motifs near breakpoints, incorporation of nontemplated sequence at junctions, approximately 30-fold enrichment at promoters and enhancers of genes actively transcribed in B-cell development, and an unexpectedly high ratio of recurrent to nonrecurrent structural variants. Single-cell tracking showed that this mechanism is active throughout leukemic evolution, with evidence of localized clustering and reiterated deletions. Integration of data on point mutations and rearrangements identified ATF7IP (<a href="/entry/613644">613644</a>) and MGA (<a href="/entry/616061">616061</a>) as tumor-suppressor genes in ALL. <a href="#24" class="mim-tip-reference" title="Papaemmanuil, E., Rapado, I., Li, Y., Potter, N. E., Wedge, D. C., Tubio, J., Alexandrov, L. B., Van Loo, P., Cooke, S. L., Marshall, J., Martincorena, I., Hinton, J., and 25 others. <strong>RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia.</strong> Nature Genet. 46: 116-125, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24413735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24413735</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24413735[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.2874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24413735">Papaemmanuil et al. (2014)</a> concluded that a remarkably parsimonious mutational process transforms ETV6/RUNX1-positive lymphoblasts, targeting the promoters, enhancers, and first exons of genes that normally regulate B-cell differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24413735" 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>Cytogenetic abnormalities involving the short arm of chromosome 12 have been documented in a wide variety of hematopoietic malignancies, including acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia, and myelodysplastic syndromes. Among 20 patients with 12q deletions or translocations, <a href="#16" class="mim-tip-reference" title="Kobayashi, H., Montgomery, K. T., Bohlander, S. K., Adra, C. N., Lim, B. L., Kucherlapati, R. S., Donis-Keller, H., Holt, M. S., Le Beau, M. M., Rowley, J. D. <strong>Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases.</strong> Blood 84: 3473-3482, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7949101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7949101</a>]" pmid="7949101">Kobayashi et al. (1994)</a> showed that most changes were clustered within a 1.39-Mb region, suggesting that a single gene on 12p13 was affected in these leukemias. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7949101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Raynaud, S. D., Baens, M., Grosgeorge, J., Rodgers, K., Reid, C. D. L., Dainton, M., Dyer, M., Fuzibet, J. G., Gratecos, N., Taillan, B., Ayraud, N., Marynen, P. <strong>Fluorescence in situ hybridization analysis of t(3;12)(q26;p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes.</strong> Blood 88: 682-689, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8695816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8695816</a>]" pmid="8695816">Raynaud et al. (1996)</a> reported 5 patients with an identical reciprocal translocation between 3q26 and 12p13. This nonrandom cytogenetic change was observed in 4 patients with myelodysplastic syndrome rapidly progressing to acute myeloid leukemia and was found at blast crisis of 1 patient with Philadelphia chromosome-positive CML. The abnormality was associated with a very poor prognosis. Fluorescence in situ hybridization with 3q26 and 12p13 probes was performed on metaphases from these 5 patients. The results were consistent with scattering of the breakpoints previously described in 3q26 rearrangements. Breakpoints at 12p13 involved the ETV6 gene in 3 myelodysplastic syndrome cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8695816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Berger, R., Le Coniat, M., Lacronique, V., Daniel, M.-T., Lessard, M., Berthou, C., Marynen, P., Bernard, O. <strong>Chromosome abnormalities of the short arm of chromosome 12 in hematopoietic malignancies: a report including three novel translocations involving the TEL/ETV6 gene.</strong> Leukemia 11: 1400-1403, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9305591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9305591</a>] [<a href="https://doi.org/10.1038/sj.leu.2400785" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9305591">Berger et al. (1997)</a> described 3 novel translocations involving the TEL/ETV6 gene on chromosome 12: t(X;12)(q28;p13), t(1;12)(q21;p13), and t(9;12)(p23-24;p13). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9305591" 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="#8" class="mim-tip-reference" title="Cave, H., Cacheux, V., Raynaud, S., Brunie, G., Bakkus, M., Cochaux, P., Preudhomme, C., Lai, J. L., Vilmer, E., Grandchamp, B. <strong>ETV6 is the target of chromosome 12p deletions in t(12;21) childhood acute lymphocytic leukemia.</strong> Leukemia 11: 1459-1464, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9305598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9305598</a>] [<a href="https://doi.org/10.1038/sj.leu.2400798" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9305598">Cave et al. (1997)</a> demonstrated that ETV6 is a target of chromosome 12p deletions in t(12;21) childhood acute lymphocytic leukemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9305598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Odero, M. D., Carlson, K., Calasanz, M. J., Lahortiga, I., Chinwalla, V., Rowley, J. D. <strong>Identification of new translocations involving ETV6 in hematologic malignancies by fluorescence in situ hybridization and spectral karyotyping.</strong> Genes Chromosomes Cancer 31: 134-142, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11319801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11319801</a>] [<a href="https://doi.org/10.1002/gcc.1127" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11319801">Odero et al. (2001)</a> stated that 35 different chromosome bands had been involved in ETV6 translocations, of which 13 had been cloned. Adding further data, they concluded that ETV6 is involved in 41 translocations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11319801" 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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In affected members of 3 unrelated families with autosomal dominant thrombocytopenia-5 (THC5; <a href="/entry/616216">616216</a>) and increased susceptibility to hematopoietic malignancies, <a href="#37" class="mim-tip-reference" title="Zhang, M. Y., Churpek, J. E., Keel, S. B., Walsh, T., Lee, M. K., Loeb, K. R., Gulsuner, S., Pritchard, C. C., Sanchez-Bonilla, M., Delrow, J. L., Basom, R. S., Forouhar, M., and 14 others. <strong>Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.</strong> Nature Genet. 47: 180-185, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25581430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25581430</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25581430[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25581430">Zhang et al. (2015)</a> identified 3 different missense mutations in the ETV6 gene (<a href="#0003">600618.0003</a>-<a href="#0005">600618.0005</a>). The mutation in the first family was found by whole-exome sequencing. Functional studies showed that the mutations abrogated DNA binding, altered subcellular localization of ETV6, decreased transcriptional repression in a dominant-negative fashion, and impaired hematopoiesis. These findings identified a central role for ETV6 in hematopoiesis and malignant transformation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25581430" 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 affected members of 3 unrelated families with THC5, <a href="#20" class="mim-tip-reference" title="Noetzli, L., Lo, R. W., Lee-Sherick, A. B., Callaghan, M., Noris, P., Savoia, A., Rajpurkar, M., Jones, K., Gowan, K., Balduini, C. L., Pecci, A., Gnan, C., and 16 others. <strong>Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia.</strong> Nature Genet. 47: 535-538, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25807284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25807284</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25807284[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25807284">Noetzli et al. (2015)</a> identified 2 different heterozygous mutations in the ETV6 gene (P214L, <a href="#0005">600618.0005</a> and R418G, <a href="#0006">600618.0006</a>). The mutation in the first family was found by whole-exome sequencing; the mutations in the 2 subsequent families were found by direct sequencing of the ETV6 gene in 23 families with a similar phenotype. Functional studies showed that all mutations resulted in decreased transcriptional repression, impaired megakaryocyte maturation, and aberrant cellular localization of mutant and wildtype ETV6, consistent with a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25807284" 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>Somatic Mutations</em></strong></p><p>
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<a href="#4" class="mim-tip-reference" title="Barjesteh van Waalwijk van Doorn-Khosrovani, S., Spensberger, D., de Knegt, Y., Tang, M., Lowenberg, B., Delwel, R. <strong>Somatic heterozygous mutations in ETV6 (TEL) and frequent absence of ETV6 protein in acute myeloid leukemia.</strong> Oncogene 24: 4129-4137, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15806161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15806161</a>] [<a href="https://doi.org/10.1038/sj.onc.1208588" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15806161">Barjesteh van Waalwijk van Doorn-Khosrovani et al. (2005)</a> analyzed 300 patients newly diagnosed with acute myeloid leukemia (AML; <a href="/entry/601626">601626</a>) for mutations in the coding region of the ETV6 gene and identified 5 somatic heterozygous mutations affecting either the homodimerization or the DNA-binding domain (e.g., <a href="#0001">600618.0001</a> and <a href="#0002">600618.0002</a>). These ETV6 mutant proteins were unable to repress transcription and showed dominant-negative effects. The authors also examined ETV6 protein expression in 77 patients with AML and found that 24 (31%) lacked the wildtype 57- and 50-kD proteins; there was no correlation between ETV6 mRNA transcript levels and the loss of ETV6 protein, suggesting posttranscriptional regulation of ETV6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15806161" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#23" class="mim-tip-reference" title="Papadopoulos, P., Ridge, S. A., Boucher, C. A., Stocking, C., Wiedemann, L. M. <strong>The novel activation of ABL by fusion to an ets-related gene, TEL.</strong> Cancer Res. 55: 34-38, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7805037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7805037</a>]" pmid="7805037">Papadopoulos et al. (1995)</a> identified a case of ALL with a previously undescribed fusion between the TEL gene and the ABL gene (<a href="/entry/189980">189980</a>) on chromosome 9q. The fusion protein showed elevated tyrosine kinase activity. However, <a href="#14" class="mim-tip-reference" title="Janssen, J. W. G., Ridge, S. A., Papadopoulos, P., Cotter, F., Ludwig, W.-D., Fonatsch, C., Rieder, H., Ostertag, W., Bartram, C. R., Wiedemann, L. M. <strong>The fusion of TEL and ABL in human acute lymphoblastic leukaemia is a rare event.</strong> Brit. J. Haemat. 90: 222-224, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7786792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7786792</a>] [<a href="https://doi.org/10.1111/j.1365-2141.1995.tb03407.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7786792">Janssen et al. (1995)</a> did not identify any TEL/ABL fusion products using RT-PCR to screen 186 adult ALL and 30 childhood ALL patients. <a href="#19" class="mim-tip-reference" title="Nilsson, T., Andreasson, P., Hoglund, M., Fioretos, T., Billstrom, R., Garwicz, S., Mitelman, F., Johansson, B. <strong>ETV6/ABL fusion is rare in Ph-negative chronic myeloid disorders.</strong> Leukemia 12: 1167-1168, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9665207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9665207</a>] [<a href="https://doi.org/10.1038/sj.leu.2401091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9665207">Nilsson et al. (1998)</a> also found no instance of ETV6/ABL fusion. in a study of a group of 67 cases of chronic myeloid disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9665207+7786792+7805037" 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 gene targeting in mice, <a href="#34" class="mim-tip-reference" title="Wang, L. C., Kuo, F., Fujiwara, Y., Gilliland, D. G., Golub, T. R., Orkin, S. H. <strong>Yolk sac angiogenic defect and intra-embryonic apoptosis in mice lacking the Ets-related factor TEL.</strong> EMBO J. 16: 4374-4383, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9250681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9250681</a>] [<a href="https://doi.org/10.1093/emboj/16.14.4374" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9250681">Wang et al. (1997)</a> showed that Tel function is required for viability of the developing mouse. The Tel -/- mice suffered a yolk sac angiogenic defect; Tel also appeared essential for the survival of selected neural and mesenchymal populations within the embryo proper. <a href="#35" class="mim-tip-reference" title="Wang, L. C., Swat, W., Fujiwara, Y., Davdison, L., Visvader, J., Kuo, F., Alt, F. W., Gilliland, D. G., Golub, T. R., Orkin, S. H. <strong>The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow.</strong> Genes Dev. 12: 2392-2401, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9694803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9694803</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9694803[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1101/gad.12.15.2392" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9694803">Wang et al. (1998)</a> generated mouse chimeras with Tel -/- embryonic stem cells to examine a possible requirement in adult hematopoiesis. They found that although Tel function is not required for the intrinsic proliferation and/or differentiation of adult-type hematopoietic lineages in the yolk sac and fetal liver, it is essential for the establishment of hematopoiesis of all lineages in the bone marrow. These findings established TEL as the first transcription factor required specifically for hematopoiesis within the bone marrow, as opposed to other sites of hematopoietic activity during development. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9250681+9694803" 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>STAT5 (see STAT5A, <a href="/entry/601511">601511</a>; STAT5B, <a href="/entry/604260">604260</a>) is activated in a broad spectrum of human hematologic malignancies. Using a genetic approach, <a href="#31" class="mim-tip-reference" title="Schwaller, J., Parganas, E., Wang, D., Cain, D., Aster, J. C., Williams, I. R., Lee, C.-K., Gerthner, R., Kitamura, T., Frantsve, J., Anastasiadou, E., Loh, M. L., Levy, D. E., Ihle, J. N., Gilliland, D. G. <strong>Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2.</strong> Molec. Cell 6: 693-704, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030348</a>] [<a href="https://doi.org/10.1016/s1097-2765(00)00067-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11030348">Schwaller et al. (2000)</a> addressed whether activation of STAT5 is necessary for the myelo- and lymphoproliferative disease induced by the TEL/JAK2 (<a href="/entry/147796">147796</a>) fusion gene. Whereas mice transplanted with bone marrow transduced with retrovirus expressing TEL/JAK2 developed a rapidly fatal myelo- and lymphoproliferative syndrome, reconstitution with bone marrow derived from Stat5a/b-deficient mice expressing TEL/JAK2 did not induce disease. Disease induction in the Stat5a/b-deficient background was rescued with a bicistronic retrovirus encoding TEL/JAK2 and Stat5a. Furthermore, myeloproliferative disease was induced by reconstitution with bone marrow cells expressing a constitutively active mutant, Stat5a, or a single Stat5a target, murine oncostatin M (OSM; <a href="/entry/165095">165095</a>). These data defined a critical role for STAT5A/B and OSM in the pathogenesis of TEL/JAK2 disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11030348" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Montpetit, A., Sinnett, D. <strong>Comparative analysis of the ETV6 gene in vertebrate genomes from pufferfish to human.</strong> Oncogene 20: 3437-3442, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11423994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11423994</a>] [<a href="https://doi.org/10.1038/sj.onc.1204444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11423994">Montpetit and Sinnett (2001)</a> reported a comparative analysis of the ETV6 gene in vertebrate genomes. They cloned the homolog of ETV6 from the compact genome of the pufferfish Fugu rubripes. In that organism the gene, composed of 8 exons, spans about 15 kb and is 16 times smaller than its human counterpart, mainly because of reduced intron size. Three of the 7 introns were unusually large (more than 2 kb). As expected, the PNT and ETS domains were highly conserved from Fugu to human. There were also conserved putative regulatory elements in the promoter as well as in the large intron 2 of Fugu ETV6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11423994" 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>Creation of the TEL/AML1 fusion disrupts 1 copy of the TEL gene and 1 copy of the AML1 gene; loss of one or the other is associated with cases of acute leukemia without the presence of the TEL/AML1 fusion gene. To determine if TEL/AML1 can contribute to leukemogenesis, <a href="#6" class="mim-tip-reference" title="Bernardin, F., Yang, Y., Cleaves, R., Zahurak, M., Cheng, L., Civin, C. I., Friedman, A. D. <strong>TEL-AML1, expressed from t(12;21) in human acute lymphocytic leukemia, induces acute leukemia in mice.</strong> Cancer Res. 62: 3904-3908, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12124316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12124316</a>]" pmid="12124316">Bernardin et al. (2002)</a> transduced marrow from C57BL/6 mice with a retroviral vector expressing TEL/AML1 or with a control vector. Two of the 9 TEL/AML1 mice developed ALL, whereas none of the 20 control mice developed leukemia. <a href="#6" class="mim-tip-reference" title="Bernardin, F., Yang, Y., Cleaves, R., Zahurak, M., Cheng, L., Civin, C. I., Friedman, A. D. <strong>TEL-AML1, expressed from t(12;21) in human acute lymphocytic leukemia, induces acute leukemia in mice.</strong> Cancer Res. 62: 3904-3908, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12124316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12124316</a>]" pmid="12124316">Bernardin et al. (2002)</a> also used the TEL/AML1 vector to transduce marrow from C57BL/6 mice lacking the overlapping p16(INK4a)p19(ARF) genes (<a href="/entry/600160">600160</a>) and transplanted the cells into wildtype recipients. No control mice died, but 6 of 8 TEL/AML1/p16p19 mice died with leukemia. These findings indicated that TEL/AML1 contributes to leukemogenesis and may cooperate with loss of p16p19 to transform lymphoid progenitors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12124316" 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="#33" class="mim-tip-reference" title="Tsuzuki, S., Seto, M., Greaves, M., Enver, T. <strong>Modeling first-hit functions of the t(12;21) TEL-AML1 translocation in mice.</strong> Proc. Nat. Acad. Sci. 101: 8443-8448, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15155899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15155899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15155899[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0402063101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15155899">Tsuzuki et al. (2004)</a> analyzed hemopoiesis in mice syngeneically transplanted with TEL/AML1-transduced bone marrow stem cells. TEL/AML1 expression was associated with an accumulation/expansion of primitive Kit (<a href="/entry/164920">164920</a>)-positive multipotent progenitors and a modest increase in myeloid colony-forming cells. TEL/AML1 expression was, however, permissive for myeloid differentiation. Analysis of B lymphopoiesis revealed an increase in early pro-B cells but a differentiation deficit beyond that stage, which resulted in lower B-cell production in the marrow. TEL/AML1-positive B-cell progenitors exhibited reduced expression of genes crucial for the pro-B to pre-B cell transition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15155899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In leukemic blast cells of a patient with acute myeloid leukemia (<a href="/entry/601626">601626</a>), <a href="#4" class="mim-tip-reference" title="Barjesteh van Waalwijk van Doorn-Khosrovani, S., Spensberger, D., de Knegt, Y., Tang, M., Lowenberg, B., Delwel, R. <strong>Somatic heterozygous mutations in ETV6 (TEL) and frequent absence of ETV6 protein in acute myeloid leukemia.</strong> Oncogene 24: 4129-4137, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15806161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15806161</a>] [<a href="https://doi.org/10.1038/sj.onc.1208588" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15806161">Barjesteh van Waalwijk van Doorn-Khosrovani et al. (2005)</a> identified a somatic heterozygous 3-bp insertion (1307insGGG) in the ETV6 gene, resulting in the insertion of a glycine between codons 344 and 345 in the DNA binding domain. The mutant protein was unable to repress transcription and showed dominant-negative effects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15806161" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs724159945 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs724159945;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs724159945?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs724159945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs724159945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000149802 OR RCV000157609 OR RCV001824288" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149802, RCV000157609, RCV001824288" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149802...</a>
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<p>In a woman and her 3 children with thrombocytopenia-5 (THC5; <a href="/entry/616216">616216</a>), <a href="#37" class="mim-tip-reference" title="Zhang, M. Y., Churpek, J. E., Keel, S. B., Walsh, T., Lee, M. K., Loeb, K. R., Gulsuner, S., Pritchard, C. C., Sanchez-Bonilla, M., Delrow, J. L., Basom, R. S., Forouhar, M., and 14 others. <strong>Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.</strong> Nature Genet. 47: 180-185, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25581430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25581430</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25581430[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25581430">Zhang et al. (2015)</a> identified a heterozygous c.1195C-T transition in the ETV6 gene, resulting in an arg399-to-cys (R399C) substitution at a highly conserved residue in the third alpha-helix of the ETS DNA-binding domain; R399 directly contacts DNA via hydrogen bonds. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the phenotype in the family and was not present in the dbSNP (build 139), 1000 Genomes Project, or Exome Variant Server databases. In vitro electrophoretic studies indicated that the mutation abrogated DNA binding, and functional studies showed that it lost normal transcriptional repression activity in a dominant-negative manner by interfering with homooligomerization. The mutant protein also showed reduced nuclear localization compared to wildtype and impaired hematopoiesis. The family was of German and Native American ancestry; 3 mutation carriers developed hematologic malignancies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25581430" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs724159946 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs724159946;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs724159946" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs724159946" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000149803 OR RCV000157610 OR RCV003162607 OR RCV003372620 OR RCV003415987" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149803, RCV000157610, RCV003162607, RCV003372620, RCV003415987" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149803...</a>
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<p>In 5 affected members of a family of Scottish descent with THC5 (<a href="/entry/616216">616216</a>), <a href="#37" class="mim-tip-reference" title="Zhang, M. Y., Churpek, J. E., Keel, S. B., Walsh, T., Lee, M. K., Loeb, K. R., Gulsuner, S., Pritchard, C. C., Sanchez-Bonilla, M., Delrow, J. L., Basom, R. S., Forouhar, M., and 14 others. <strong>Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.</strong> Nature Genet. 47: 180-185, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25581430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25581430</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25581430[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25581430">Zhang et al. (2015)</a> identified a heterozygous c.1106G-A transition in the ETV6 gene, resulting in an arg369-to-gln (R369Q) substitution at a highly conserved residue in the second beta-sheet of the ETS DNA-binding domain. The mutation was not present in the dbSNP (build 139), 1000 Genomes Project, or Exome Variant Server databases. In vitro electrophoretic studies indicated that the mutation abrogated DNA binding, and functional studies showed that it lost normal transcriptional repression activity in a dominant-negative manner by interfering with homo-oligomerization. The mutant protein also showed reduced nuclear localization compared to wildtype and impaired hematopoiesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25581430" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs724159947 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs724159947;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs724159947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs724159947" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000149804 OR RCV000157611 OR RCV001281572 OR RCV001818340" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149804, RCV000157611, RCV001281572, RCV001818340" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149804...</a>
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<p>In an African American woman with thrombocytopenia-5 (THC5; <a href="/entry/616216">616216</a>) who developed mixed T-cell/myeloid acute leukemia, <a href="#37" class="mim-tip-reference" title="Zhang, M. Y., Churpek, J. E., Keel, S. B., Walsh, T., Lee, M. K., Loeb, K. R., Gulsuner, S., Pritchard, C. C., Sanchez-Bonilla, M., Delrow, J. L., Basom, R. S., Forouhar, M., and 14 others. <strong>Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.</strong> Nature Genet. 47: 180-185, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25581430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25581430</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25581430[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3177" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25581430">Zhang et al. (2015)</a> identified a heterozygous c.641C-T transition in the ETV6 gene, resulting in a pro214-to-leu (P214L) substitution at a highly conserved residue in a linker inhibitory domain that indirectly promotes DNA binding. The mutation was not present in the dbSNP (build 139), 1000 Genomes Project, or Exome Variant Server databases. Expression of the mutation in HeLa cells showed that the mutant protein had predominantly cytoplasmic localization, rather than normal nuclear localization. The mutant protein also impaired hematopoiesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25581430" 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 affected members of a family with THC5, <a href="#20" class="mim-tip-reference" title="Noetzli, L., Lo, R. W., Lee-Sherick, A. B., Callaghan, M., Noris, P., Savoia, A., Rajpurkar, M., Jones, K., Gowan, K., Balduini, C. L., Pecci, A., Gnan, C., and 16 others. <strong>Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia.</strong> Nature Genet. 47: 535-538, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25807284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25807284</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25807284[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25807284">Noetzli et al. (2015)</a> identified heterozygosity for the c.641C-T transition (c.641C-T, NM_001987) in the ETV6 gene, resulting in a P214L substitution. The mutation was found by whole-exome sequencing and segregated with the disorder in the family. Direct screening of the ETV6 gene in 23 additional families with autosomal dominant thrombocytopenia identified 1 family with the same P214L mutation. Three patients from the 2 families developed B-cell leukemia. In vitro functional expression studies showed that the P214L mutant protein had less transcriptional repression activity than wildtype. Transfection of the mutation into CD34+ cells cultured with thrombopoietin resulted in delayed and decreased megakaryocyte maturation compared to control cells. There was aberrant cytoplasmic localization of both the mutant and wildtype protein, consistent with a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25807284" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786205226 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205226;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs786205226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs786205226" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000170497 OR RCV004020022" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170497, RCV004020022" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170497...</a>
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<p>In affected members of a family with autosomal dominant thrombocytopenia-5 (THC5; <a href="/entry/616216">616216</a>), <a href="#20" class="mim-tip-reference" title="Noetzli, L., Lo, R. W., Lee-Sherick, A. B., Callaghan, M., Noris, P., Savoia, A., Rajpurkar, M., Jones, K., Gowan, K., Balduini, C. L., Pecci, A., Gnan, C., and 16 others. <strong>Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia.</strong> Nature Genet. 47: 535-538, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25807284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25807284</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25807284[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng.3253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25807284">Noetzli et al. (2015)</a> identified a heterozygous c.1252A-G transition (c.1252A-G, NM_001987) in the last codon of exon 7 of the ETV6 gene, predicted to result in an arg418-to-gly (R418G) substitution at a highly conserved residue in the DNA-binding domain. Analysis of patient cells showed that the mutation also disrupted a splice site, resulting in an alternatively spliced product with the skipping of exon 7, a partial deletion of the putative DNA-binding domain (385_418del), and a subsequent frameshift and premature termination (Asn385ValfsTer7). The truncated protein was expressed in transfected HEK293T cells, but not in patient platelets. The mutation was not found in the 1000 Genomes Project database. In vitro functional expression studies showed that both the R418G mutant protein and the truncated protein had less transcriptional repression activity than wildtype. Transfection of the R418G mutation into CD34+ cells cultured with thrombopoietin resulted in delayed and decreased megakaryocyte maturation compared to control cells. There was aberrant cytoplasmic localization of both the mutant and wildtype protein, consistent with a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25807284" 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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Anderson, K., Lutz, C., van Delft, F. W., Bateman, C. M., Guo, Y., Colman, S. M., Kempski, H., Moorman, A. V., Titley, I., Swansbury, J., Kearney, L., Enver, T., Greaves, M.
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<strong>Genetic variegation of clonal architecture and propagating cells in leukaemia.</strong>
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Nature 469: 356-361, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21160474/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21160474</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21160474" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature09650" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Apperley2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Apperley, J. F., Gardembas, M., Melo, J. V., Russell-Jones, R., Bain, B. J., Baxter, E. J., Chase, A., Chessells, J. M., Colombat, M., Dearden, C. E., Dimitrijevic, S., Mahon, F.-X., Marin, D., Nikolova, Z., Olavarria, E., Silberman, S., Schultheis, B., Cross, N. C. P., Goldman, J. M.
|
|
<strong>Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta.</strong>
|
|
New Eng. J. Med. 347: 481-487, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12181402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12181402</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12181402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMoa020150" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Baens1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Baens, M., Peeters, P., Guo, C., Aerssens, J., Marynen, P.
|
|
<strong>Genomic organization of TEL: the human ETS-variant gene 6.</strong>
|
|
Genome Res. 6: 404-413, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8743990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8743990</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8743990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gr.6.5.404" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Barjesteh van Waalwijk van Doorn-Khosrovani2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Barjesteh van Waalwijk van Doorn-Khosrovani, S., Spensberger, D., de Knegt, Y., Tang, M., Lowenberg, B., Delwel, R.
|
|
<strong>Somatic heterozygous mutations in ETV6 (TEL) and frequent absence of ETV6 protein in acute myeloid leukemia.</strong>
|
|
Oncogene 24: 4129-4137, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15806161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15806161</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15806161" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.onc.1208588" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Berger1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Berger, R., Le Coniat, M., Lacronique, V., Daniel, M.-T., Lessard, M., Berthou, C., Marynen, P., Bernard, O.
|
|
<strong>Chromosome abnormalities of the short arm of chromosome 12 in hematopoietic malignancies: a report including three novel translocations involving the TEL/ETV6 gene.</strong>
|
|
Leukemia 11: 1400-1403, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9305591/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9305591</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9305591" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.leu.2400785" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Bernardin2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bernardin, F., Yang, Y., Cleaves, R., Zahurak, M., Cheng, L., Civin, C. I., Friedman, A. D.
|
|
<strong>TEL-AML1, expressed from t(12;21) in human acute lymphocytic leukemia, induces acute leukemia in mice.</strong>
|
|
Cancer Res. 62: 3904-3908, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12124316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12124316</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12124316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Buijs1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Buijs, A., Sherr, S., van Baal, S., van Bezouw, S., van der Plas, D., Geurts van Kessel, A., Riegman, P., Lekanne Deprez, R., Zwarthoff, E., Hagemeijer, A., Grosveld, G.
|
|
<strong>Translocation (12;22)(p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12q13 to the MN1 gene on 22q11.</strong>
|
|
Oncogene 10: 1511-1519, 1995. Note: Erratum: Oncogene 11: 809 only, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7731705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7731705</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7731705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Cave1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cave, H., Cacheux, V., Raynaud, S., Brunie, G., Bakkus, M., Cochaux, P., Preudhomme, C., Lai, J. L., Vilmer, E., Grandchamp, B.
|
|
<strong>ETV6 is the target of chromosome 12p deletions in t(12;21) childhood acute lymphocytic leukemia.</strong>
|
|
Leukemia 11: 1459-1464, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9305598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9305598</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9305598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.leu.2400798" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Cazzaniga1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cazzaniga, G., Tosi, S., Aloisi, A., Giudici, G., Daniotti, M., Pioltelli, P., Kearney, L., Biondi, A.
|
|
<strong>The tyrosine kinase Abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts.</strong>
|
|
Blood 94: 4370-4373, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10590083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10590083</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10590083" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Cools1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cools, J., Bilhou-Nabera, C., Wlodarska, I., Cabrol, C., Talmant, P., Bernard, P., Hagemeijer, A., Marynen, P.
|
|
<strong>Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13).</strong>
|
|
Blood 94: 1820-1824, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10477709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10477709</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10477709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Ford1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ford, A. M., Bennett, C. A., Price, C. M., Bruin, M. C. A., Van Wering, E. R., Greaves, M.
|
|
<strong>Fetal origins of the TEL-AML1 fusion gene in identical twins with leukemia.</strong>
|
|
Proc. Nat. Acad. Sci. 95: 4584-4588, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9539781/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9539781</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9539781[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9539781" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.95.8.4584" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Golub1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Golub, T. R., Barker, G. F., Bohlander, S. K., Hiebert, S. W., Ward, D. C., Bray-Ward, P., Morgan, E., Raimondi, S. C., Rowley, J. D., Gilliland, D. G.
|
|
<strong>Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia.</strong>
|
|
Proc. Nat. Acad. Sci. 92: 4917-4921, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7761424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7761424</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7761424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.92.11.4917" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Golub1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Golub, T. R., Barker, G. F., Lovett, M., Gilliland, D. G.
|
|
<strong>Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation.</strong>
|
|
Cell 77: 307-316, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8168137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8168137</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8168137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0092-8674(94)90322-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Janssen1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Janssen, J. W. G., Ridge, S. A., Papadopoulos, P., Cotter, F., Ludwig, W.-D., Fonatsch, C., Rieder, H., Ostertag, W., Bartram, C. R., Wiedemann, L. M.
|
|
<strong>The fusion of TEL and ABL in human acute lymphoblastic leukaemia is a rare event.</strong>
|
|
Brit. J. Haemat. 90: 222-224, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7786792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7786792</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7786792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.1995.tb03407.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Knezevich1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Knezevich, S. R., McFadden, D. E., Tao, W., Lim, J. F., Sorensen, P. H. B.
|
|
<strong>A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma.</strong>
|
|
Nature Genet. 18: 184-187, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9462753/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9462753</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9462753" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng0298-184" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Kobayashi1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kobayashi, H., Montgomery, K. T., Bohlander, S. K., Adra, C. N., Lim, B. L., Kucherlapati, R. S., Donis-Keller, H., Holt, M. S., Le Beau, M. M., Rowley, J. D.
|
|
<strong>Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases.</strong>
|
|
Blood 84: 3473-3482, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7949101/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7949101</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7949101" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Lacronique1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lacronique, V., Boureux, A., Della Valle, V., Poirel, H., Quang, C. T., Mauchauffe, M., Berthou, C., Lessard, M., Berger, R., Ghysdael, J., Bernard, O. A.
|
|
<strong>A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia.</strong>
|
|
Science 278: 1309-1312, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9360930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9360930</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9360930" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.278.5341.1309" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Montpetit2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Montpetit, A., Sinnett, D.
|
|
<strong>Comparative analysis of the ETV6 gene in vertebrate genomes from pufferfish to human.</strong>
|
|
Oncogene 20: 3437-3442, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11423994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11423994</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11423994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.onc.1204444" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Nilsson1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Nilsson, T., Andreasson, P., Hoglund, M., Fioretos, T., Billstrom, R., Garwicz, S., Mitelman, F., Johansson, B.
|
|
<strong>ETV6/ABL fusion is rare in Ph-negative chronic myeloid disorders.</strong>
|
|
Leukemia 12: 1167-1168, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9665207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9665207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9665207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.leu.2401091" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Noetzli2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Noetzli, L., Lo, R. W., Lee-Sherick, A. B., Callaghan, M., Noris, P., Savoia, A., Rajpurkar, M., Jones, K., Gowan, K., Balduini, C. L., Pecci, A., Gnan, C., and 16 others.
|
|
<strong>Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia.</strong>
|
|
Nature Genet. 47: 535-538, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25807284/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25807284</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25807284[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25807284" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng.3253" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Odero2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Odero, M. D., Carlson, K., Calasanz, M. J., Lahortiga, I., Chinwalla, V., Rowley, J. D.
|
|
<strong>Identification of new translocations involving ETV6 in hematologic malignancies by fluorescence in situ hybridization and spectral karyotyping.</strong>
|
|
Genes Chromosomes Cancer 31: 134-142, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11319801/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11319801</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11319801" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/gcc.1127" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Odero2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Odero, M. D., Vizmanos, J. L., Roman, J. P., Lahortiga, I., Panizo, C., Calasanz, M. J., Zeleznik-Le, N. J., Rowley, J. D., Novo, F. J.
|
|
<strong>A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a patient with myelodysplastic syndrome.</strong>
|
|
Genes Chromosomes Cancer 35: 11-19, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12203785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12203785</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12203785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/gcc.10090" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Papadopoulos1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Papadopoulos, P., Ridge, S. A., Boucher, C. A., Stocking, C., Wiedemann, L. M.
|
|
<strong>The novel activation of ABL by fusion to an ets-related gene, TEL.</strong>
|
|
Cancer Res. 55: 34-38, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7805037/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7805037</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7805037" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Papaemmanuil2014" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Papaemmanuil, E., Rapado, I., Li, Y., Potter, N. E., Wedge, D. C., Tubio, J., Alexandrov, L. B., Van Loo, P., Cooke, S. L., Marshall, J., Martincorena, I., Hinton, J., and 25 others.
|
|
<strong>RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia.</strong>
|
|
Nature Genet. 46: 116-125, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24413735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24413735</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24413735[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24413735" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng.2874" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Peeters1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Peeters, P., Raynaud, S. D., Cools, J., Wlodarska, I., Grosgeorge, J., Philip, P., Monpoux, F., Van Rompaey, L., Baens, M., Van den Berghe, H., Marynen, P.
|
|
<strong>Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia.</strong>
|
|
Blood 90: 2535-2540, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9326218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9326218</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9326218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Penas2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Penas, E. M. M., Cools, J., Algenstaedt, P., Hinz, K., Seeger, D., Schafhausen, P., Schilling, G., Marynen, P., Hossfeld, D. K., Dierlamm, J.
|
|
<strong>A novel cryptic translocation t(12;17)(p13;p12-p13) in a secondary acute myeloid leukemia results in a fusion of the ETV6 gene and the antisense strand of the PER1 gene.</strong>
|
|
Genes Chromosomes Cancer 37: 79-83, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12661008/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12661008</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12661008" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/gcc.10175" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Pierce2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pierce, A., Carney, L., Hamza, H. G., Griffiths, J. R., Zhang, L., Whetton, B. A., Gonzalez Sanchez, M. B., Tamura, T., Sternberg, D., Whetton, A. D.
|
|
<strong>THOC5 spliceosome protein: a target for leukaemogenic tyrosine kinases that affects inositol lipid turnover.</strong>
|
|
Brit. J. Haemat. 141: 641-650, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18373705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18373705</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18373705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1111/j.1365-2141.2008.07090.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Raynaud1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Raynaud, S. D., Baens, M., Grosgeorge, J., Rodgers, K., Reid, C. D. L., Dainton, M., Dyer, M., Fuzibet, J. G., Gratecos, N., Taillan, B., Ayraud, N., Marynen, P.
|
|
<strong>Fluorescence in situ hybridization analysis of t(3;12)(q26;p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes.</strong>
|
|
Blood 88: 682-689, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8695816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8695816</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8695816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Romana1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Romana, S. P., Poirel, H., Leconiat, M., Flexor, M.-A., Mauchauffe, M., Jonveaux, P., Macintyre, E. A., Berger, R., Bernard, O. A.
|
|
<strong>High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia.</strong>
|
|
Blood 86: 4263-4269, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7492786/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7492786</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7492786" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Salomon-Nguyen2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Salomon-Nguyen, F., Della-Valle, V., Mauchauffe, M., Busson-Le Coniat, M., Ghysdael, J., Berger, R., Bernard, O. A.
|
|
<strong>The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 6757-6762, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10829078/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10829078</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10829078[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10829078" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.120162297" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Schwaller2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Schwaller, J., Parganas, E., Wang, D., Cain, D., Aster, J. C., Williams, I. R., Lee, C.-K., Gerthner, R., Kitamura, T., Frantsve, J., Anastasiadou, E., Loh, M. L., Levy, D. E., Ihle, J. N., Gilliland, D. G.
|
|
<strong>Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2.</strong>
|
|
Molec. Cell 6: 693-704, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11030348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11030348</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11030348" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s1097-2765(00)00067-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Stegmaier1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Stegmaier, K., Pendse, S., Barker, G. F., Bray-Ward, P., Ward, D. C., Montgomery, K. T., Krauter, K. S., Reynolds, C., Sklar, J., Donnelly, M., Bohlander, S. K., Rowley, J. D., Sallan, S. E., Gilliland, D. G., Golub, T. R.
|
|
<strong>Frequent loss of heterozygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood.</strong>
|
|
Blood 86: 38-44, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7795247/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7795247</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7795247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Tsuzuki2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Tsuzuki, S., Seto, M., Greaves, M., Enver, T.
|
|
<strong>Modeling first-hit functions of the t(12;21) TEL-AML1 translocation in mice.</strong>
|
|
Proc. Nat. Acad. Sci. 101: 8443-8448, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15155899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15155899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15155899[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15155899" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0402063101" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Wang1997" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Wang, L. C., Kuo, F., Fujiwara, Y., Gilliland, D. G., Golub, T. R., Orkin, S. H.
|
|
<strong>Yolk sac angiogenic defect and intra-embryonic apoptosis in mice lacking the Ets-related factor TEL.</strong>
|
|
EMBO J. 16: 4374-4383, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9250681/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9250681</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9250681" 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/10.1093/emboj/16.14.4374" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
|
|
<a id="35" class="mim-anchor"></a>
|
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<a id="Wang1998" class="mim-anchor"></a>
|
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<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, L. C., Swat, W., Fujiwara, Y., Davdison, L., Visvader, J., Kuo, F., Alt, F. W., Gilliland, D. G., Golub, T. R., Orkin, S. H.
|
|
<strong>The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow.</strong>
|
|
Genes Dev. 12: 2392-2401, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9694803/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9694803</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=9694803[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9694803" 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/10.1101/gad.12.15.2392" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="36" class="mim-anchor"></a>
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<a id="Yagasaki1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Yagasaki, F., Jinnai, I., Yoshida, S., Yokoyama, Y., Matsuda, A., Kusumoto, S., Kobayashi, H., Terasaki, H., Ohyashiki, K., Asou, N., Murohashi, I., Bessho, M., Hirashima, K.
|
|
<strong>Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13).</strong>
|
|
Genes Chromosomes Cancer 26: 192-202, 1999.
|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10502316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10502316</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10502316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1002/(sici)1098-2264(199911)26:3<192::aid-gcc2>3.0.co;2-e" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="37" class="mim-anchor"></a>
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<a id="Zhang2015" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Zhang, M. Y., Churpek, J. E., Keel, S. B., Walsh, T., Lee, M. K., Loeb, K. R., Gulsuner, S., Pritchard, C. C., Sanchez-Bonilla, M., Delrow, J. L., Basom, R. S., Forouhar, M., and 14 others.
|
|
<strong>Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.</strong>
|
|
Nature Genet. 47: 180-185, 2015.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25581430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25581430</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25581430[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25581430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1038/ng.3177" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
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</span>
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
Cassandra L. Kniffin - updated : 5/12/2015
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</span>
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</div>
|
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</div>
|
|
<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">
|
|
Cassandra L. Kniffin - updated : 2/5/2015<br>Ada Hamosh - updated : 11/18/2014<br>Ada Hamosh - updated : 6/10/2011<br>Marla J. F. O'Neill - updated : 6/10/2009<br>Patricia A. Hartz - updated : 4/16/2009<br>Cassandra L. Kniffin - updated : 12/5/2008<br>Marla J. F. O'Neill - updated : 4/12/2006<br>Patricia A. Hartz - updated : 7/2/2004<br>Victor A. McKusick - updated : 7/18/2003<br>Patricia A. Hartz - updated : 10/17/2002<br>Victor A. McKusick - updated : 10/14/2002<br>Victor A. McKusick - updated : 9/16/2002<br>Victor A. McKusick - updated : 8/7/2001<br>Victor A. McKusick - updated : 6/21/2001<br>Stylianos E. Antonarakis - updated : 10/11/2000<br>Victor A. McKusick - updated : 5/5/2000<br>Victor A. McKusick - updated : 1/6/2000<br>Victor A. McKusick - updated : 11/4/1998<br>Victor A. McKusick - updated : 9/2/1998<br>Victor A. McKusick - updated : 5/21/1998<br>Victor A. McKusick - updated : 1/26/1998<br>Victor A. McKusick - updated : 11/5/1997
|
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</span>
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</div>
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</div>
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</div>
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<div>
|
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<a id="creationDate" class="mim-anchor"></a>
|
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<div class="row">
|
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
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<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
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</span>
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</div>
|
|
<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 : 9/18/1995
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
|
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
|
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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</span>
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
carol : 01/26/2021
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</span>
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</div>
|
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</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
|
<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
carol : 01/25/2021<br>carol : 12/09/2020<br>alopez : 11/01/2016<br>carol : 05/13/2015<br>mcolton : 5/12/2015<br>ckniffin : 5/12/2015<br>carol : 3/3/2015<br>carol : 2/6/2015<br>carol : 2/6/2015<br>mcolton : 2/5/2015<br>ckniffin : 2/5/2015<br>alopez : 11/18/2014<br>terry : 11/29/2012<br>alopez : 6/20/2011<br>terry : 6/10/2011<br>wwang : 6/12/2009<br>terry : 6/10/2009<br>mgross : 4/16/2009<br>wwang : 12/16/2008<br>ckniffin : 12/5/2008<br>wwang : 4/12/2006<br>terry : 4/12/2006<br>wwang : 6/17/2005<br>wwang : 6/8/2005<br>terry : 6/7/2005<br>mgross : 7/14/2004<br>terry : 7/2/2004<br>mgross : 2/3/2004<br>tkritzer : 7/30/2003<br>terry : 7/18/2003<br>carol : 6/23/2003<br>mgross : 5/30/2003<br>mgross : 10/17/2002<br>tkritzer : 10/14/2002<br>carol : 10/3/2002<br>ckniffin : 10/3/2002<br>tkritzer : 9/25/2002<br>tkritzer : 9/25/2002<br>tkritzer : 9/16/2002<br>mcapotos : 8/10/2001<br>mcapotos : 8/9/2001<br>terry : 8/7/2001<br>terry : 6/21/2001<br>carol : 1/26/2001<br>terry : 1/25/2001<br>mgross : 10/11/2000<br>carol : 8/30/2000<br>mcapotos : 8/28/2000<br>mcapotos : 8/9/2000<br>mgross : 5/5/2000<br>mcapotos : 4/25/2000<br>mgross : 1/19/2000<br>mgross : 1/19/2000<br>terry : 1/6/2000<br>carol : 11/12/1998<br>terry : 11/4/1998<br>alopez : 9/2/1998<br>terry : 6/16/1998<br>terry : 5/21/1998<br>mark : 1/26/1998<br>terry : 1/26/1998<br>terry : 11/5/1997<br>jamie : 5/29/1997<br>jenny : 12/23/1996<br>terry : 12/17/1996<br>mark : 10/3/1996<br>terry : 9/9/1996<br>mark : 4/1/1996<br>mimadm : 11/3/1995<br>mark : 9/18/1995
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 600618
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ETS VARIANT TRANSCRIPTION FACTOR 6; ETV6
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
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|
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<div>
|
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<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
ETS VARIANT GENE 6<br />
|
|
TRANSLOCATION, ETS, LEUKEMIA; TEL<br />
|
|
TEL1 ONCOGENE
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<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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<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
ETV6/PDGFRB FUSION GENE, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
ETV6/MN1 FUSION GENE, INCLUDED<br />
|
|
ETV6/AML1 FUSION GENE, INCLUDED<br />
|
|
ETV6/ARNT FUSION GENE, INCLUDED<br />
|
|
ETV6/MDS2 FUSION GENE, INCLUDED<br />
|
|
ETV6/ABL2 FUSION GENE, INCLUDED<br />
|
|
ETV6/PER1 FUSION GENE, INCLUDED<br />
|
|
ETV6/NTRK3 FUSION GENE, INCLUDED<br />
|
|
ETV6/ACS2 FUSION GENE, INCLUDED<br />
|
|
ETV6/BTL FUSION GENE, INCLUDED<br />
|
|
ETV6/JAK2 FUSION GENE, INCLUDED<br />
|
|
ETV6/RUNX1 FUSION GENE, INCLUDED
|
|
</span>
|
|
</div>
|
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</div>
|
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<div>
|
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<br />
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</div>
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</div>
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|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: ETV6</em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 12p13.2
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 12:11,649,674-11,895,377 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
12p13.2
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Leukemia, acute myeloid, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
601626
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Thrombocytopenia 5
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
616216
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
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<div>
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<br />
|
|
</div>
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|
|
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|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The ETV6 gene encodes an ETS family transcriptional repressor and is frequently rearranged or fused with other genes in human leukemias of myeloid or lymphoid origins (Wang et al., 1997; summary by Zhang et al., 2015). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
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<p>Golub et al. (1994) identified the ETV6 gene as part of a fusion transcript resulting from a somatic t(5;12)(q33;p13) translocation in chronic myelomonocytic leukemia (see 607785) cancer cells. The translocation was found to consist of a novel gene on chromosome 12p13 and the PDGFRB (173410) gene on 5q33. Golub et al. (1994) isolated clones corresponding to the coding sequence from a chromosome 12 cDNA library. Portions of the gene showed homology to the ETS family of transcription factors, and it was designated 'TEL' for translocation, ETS, leukemia. Northern blot analysis detected 3 transcripts of 6.5 kb, 4.5 kb, and 2.4 kb in all tissues examined. </p><p>Baens et al. (1996) developed contigs containing the complete coding sequence and the 5-prime and 3-prime UTRs of the ETV6 gene. The helix-loop-helix (HLH) motif is coded by exons 3 and 4, whereas exons 6 to 8 encode for the ETS DNA-binding domain. The ETV6 gene is flanked at its 5-prime and 3-prime ends by markers D12S1697 and D12S98, respectively. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</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>Baens et al. (1996) determined that the ETV6 gene contains 8 exons spanning 240 kb. They identified an alternative exon 1B located within intron 2. </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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<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>Stegmaier et al. (1995) mapped the ETV6 gene to chromosome 12p13. </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>Gene Function</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>Stegmaier et al. (1995) presented evidence that the TEL gene may act as a tumor suppressor gene. They noted noted that 5% of children with acute lymphocytic leukemia (ALL) have 12p13-p12 deletions. Using markers flanking the TEL gene, Stegmaier et al. (1995) found that 15% of 81 informative children with ALL had TEL loss of heterozygosity that was not evident on cytogenetic analysis. Detailed examination showed that the critically deleted region included 2 candidate suppressor genes: TEL and KIP (600778), the gene encoding the cyclin-dependent kinase inhibitor p27. </p><p><strong><em>ETV6/PDGFRB Fusion Gene</em></strong></p><p>
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In bone marrow cells from a 17-year-old male with chronic myelomonocytic leukemia, Golub et al. (1994) identified a somatic t(5;12)(q33;p13) translocation consisting of the 154 N terminal residues of ETV6 linked to the transmembrane and tyrosine kinase domains of the PDGFRB on chromosome 5q33. The entire ligand-binding domain of PDGFRB and the putative DNA-binding domain of ETV6 were both excluded from the fusion transcript. This same rearrangement was detected in 3 additional patients with chronic myelomonocytic leukemia. The index patient subsequently developed acute myelogenous leukemia (AML; 601626) associated with other genetic alterations, suggesting that the t(5;12)(q33;p13) translocation was an early step in a multistep progression to full AML. </p><p>Apperley et al. (2002) reported successful response to therapy with the tyrosine kinase inhibitor imatinib mesylate in 3 patients with chronic myeloproliferative disorder (131440) and a t(5;12) translocation. The patients' leukemic cells carried the ETV6/PDGFRB fusion gene. </p><p>Pierce et al. (2008) showed that expression of TEL/PDGFRB in murine myeloid FDCP-Mix cells prevented cell differentiation, increased cell survival, increased the level of phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3), and increased the expression and phosphorylation of Thoc5 (612733). Elevated Thoc5 expression also led to increased cell survival and PtdInsP3 levels, suggesting that the effects associated with TEL/PDGFRB expression were due, at least in part, to Thoc5 upregulation. </p><p><strong><em>ETV6/AML1 Fusion Gene</em></strong></p><p>
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Golub et al. (1995) documented fusion of TEL to the AML1 gene (151385) on chromosome 21 in 2 pediatric patients with acute lymphocytic leukemia with t(12;21) translocations. The findings implicated TEL in the pathogenesis of leukemia through its fusion to either a receptor tyrosine kinase, such as PDGFRB, or a transcription factor, such as AML1. </p><p>Using RT-PCR, Romana et al. (1995) identified the TEL/AML1 fusion gene in 8 (16%) of 46 childhood B-cell lymphoblastic leukemia cells, only 1 of which showed a 12p abnormality by classic cytogenetic techniques. The authors concluded that t(12;21) is the most frequent translocation in childhood B-lineage ALL. </p><p>Ford et al. (1998) reported the extraordinary case of monozygotic twins in whom common acute lymphoblastic leukemia was diagnosed at ages 3.5 years and 4 years. The twins' leukemic DNA shared the same unique (or clonotypic) but nonconstitutive TEL/AML1 fusion sequence. The most plausible explanation for this finding was thought to be a single cell origin of the TEL/AML fusion in 1 fetus in utero, probably as a leukemia-initiating mutation, followed by intraplacental metastasis of clonal progeny to the other twin. Clonal identity was further supported by the finding that the leukemic cells in the twins shared an identical rearranged IGH allele. These data had implications for the etiology and natural history of childhood leukemia. </p><p><strong><em>ETV6/MN1 Fusion Gene</em></strong></p><p>
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Buijs et al. (1995) showed that the MN1 gene (156100) on 22q11 is fused to the TEL gene in the t(12;22)(p13;q11) translocation that is observed in different myeloid malignancies. </p><p><strong><em>ETV6/JAK2 Fusion Gene</em></strong></p><p>
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Peeters et al. (1997) identified a t(9;12)(p24;p13) translocation in a patient with early pre-B acute lymphoid leukemia and a t(9;15;12)(p24;q15;p13) translocation in a patient with atypical chronic myelogenous leukemia (CML; 608232) in transformation. Both changes involved the ETV6 gene at 12p13 and the JAK2 gene (147796) at 9p24. In each case different fusion mRNAs were found, with only 1 resulting in a chimeric protein consisting of the oligomerization domain of ETV6 and the protein tyrosine kinase domain of JAK2. </p><p>Lacronique et al. (1997) observed a t(9;12)(p24;p13) translocation in leukemic cells from a 4-year-old boy with T-cell ALL. The 3-prime portion of the JAK2 gene was fused to the 5-prime portion of the ETV6 gene, resulting in a protein containing the catalytic domain of JAK2 and the oligomerization domain of ETV6. The resultant protein had constitutive tyrosine kinase activity and conferred cytokine-independent proliferation to a murine cell line. </p><p><strong><em>ETV6/NTRK3 Fusion Gene</em></strong></p><p>
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Knezevich et al. (1998) detected a recurrent t(12;15)(p13;q25) translocation consisting of fusion of the ETV6 gene with the NTRK3 gene (191316) on 15q25 in 3 congenital fibrosarcomas analyzed. Congenital (or infantile) fibrosarcoma (CFS) is a malignant tumor of fibroblasts that occurs in patients aged 2 or younger. CFS is unique among human sarcomas in that it has an excellent prognosis and very low metastatic rate. CFS is histologically identical to adult-type fibrosarcoma (ATFS); however, ATFS is an aggressive malignancy of adults and older children that has a poor prognosis. The same translocation was not identified in ATFS or infantile fibromatosis (228550), a histologically similar but benign fibroblastic proliferation occurring in the same age group as CFS. ETV6/NTRK3 fusion transcripts encoded the HLH protein dimerization domain of ETV6 fused to the protein tyrosine kinase (PTK) domain of NTRK3. Presumably, the chimeric protein tyrosine kinase contributed to oncogenesis by dysregulation of NTRK3 signal transduction pathways. </p><p><strong><em>ETV6/ACS2 Fusion Gene</em></strong></p><p>
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Yagasaki et al. (1999) identified a recurrent t(5;12)(q31;p13) translocation, resulting in an ETV6/ACS2 (604443) fusion gene in a patient with refractory anemia with excess blasts with basophilia, a patient with AML with eosinophilia, and a patient with acute eosinophilic leukemia (AEL). The ETV6/ACS2 fusion transcripts showed an out-frame fusion of exon 1 of ETV6 to exon 1 of ACS2 in the patient with AEL, an out-frame fusion of exon 1 of ETV6 to exon 11 of ACS2 in the patient with AML, and a short in-frame fusion of exon 1 of ETV6 to the 3-prime untranslated region of ACS2 in the patient with refractory anemia. Reciprocal ACS2/ETV6 transcripts were identified in 2 of the cases. FISH with ETV6 cosmids on 12p13, and BACs and PIs on 5q31, demonstrated that the 5q31 breakpoints of the AML and AEL cases involved the 5-prime portion of the ACS2 gene, and that the 5q31 breakpoint of the refractory anemia case involved the 3-prime portion of the ACS2 gene. None of the resulting chimeric transcripts except for the ACS2/ETV6 transcript in the refractory anemia case led to a fusion protein. </p><p><strong><em>ETV6/ABL2 Fusion Gene</em></strong></p><p>
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Cazzaniga et al. (1999) identified a t(1;12)(q25;p13) translocation involving the ETV6 gene and the ABL2 (164690) gene in a patient with acute myeloid leukemia M4 with eosinophilia. The novel transcript resulted in a chimeric protein consisting of the helix-loop-helix oligomerization domain of ETV6 and the SH2, SH3, and protein tyrosine kinase domains of ABL2. The reciprocal transcript ABL2/ETV6 was also detected in the patient's RNA by RT-PCR, although at a lower expression level. </p><p><strong><em>ETV6/BTL Fusion Gene</em></strong></p><p>
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Cools et al. (1999) reported 4 cases of acute myeloid leukemia with very immature myeloblasts and a t(4;12)(q11-q12;p13) translocation in which ETV6 was linked with the BTL gene (604332). RT-PCR experiments indicated that expression of the BTL/ETV6 transcript, but not of the reciprocal ETV6/BTL transcript, was a common finding in these leukemias. In contrast to most of the other ETV6 fusions, both the complete helix-loop-helix and ETS DNA-binding domains of ETV6 were present in the predicted BTL/ETV6 fusion protein, and a chimeric gene was transcribed from the BTL promoter. </p><p><strong><em>ETV6/ARNT Fusion Gene</em></strong></p><p>
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Salomon-Nguyen et al. (2000) determined that a t(1;12)(q21;p13) translocation observed in a case of acute myeloblastic leukemia (AML-M2) resulted in a fusion protein containing the amino-terminal of TEL and essentially all of the ARNT gene (126110). The involvement of ARNT in human leukemogenesis had not previously been described. </p><p><strong><em>ETV6/MDS2 Fusion Gene</em></strong></p><p>
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Odero et al. (2002) identified a t(1;12)(p36.1;p13) translocation in an MDS patient that resulted in the fusion of exons 1 and 2 of ETV6 to exons 6 and 7 of MDS2 (607305). The predicted protein is out of frame and contains the first 54 amino acids of ETV6 followed by 4 novel amino acids from the MDS2 sequence. The truncated ETV6 protein lacks critical functional domains. </p><p><strong><em>ETV6/PER1 Fusion Gene</em></strong></p><p>
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Penas et al. (2003) cloned a novel cryptic translocation, t(12;17)(p13;p12-p13), occurring in a patient with acute myeloid leukemia evolving from a chronic myelomonocytic leukemia. They identified a fusion transcript between exon 1 of the ETV6 gene and the antisense strand of PER1 (602260). The ETV6/PER1 fusion transcript did not produce a fusion protein, and no other fusion transcripts could be detected. Penas et al. (2003) hypothesized that in the absence of a fusion protein, the inactivation of PER1 or deregulation of a gene in the neighborhood of PER1 may contribute to the pathogenesis of leukemia with this translocation. </p><p><strong><em>ETV6/RUNX1 Fusion Gene</em></strong></p><p>
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Anderson et al. (2011) examined the genetic architecture of cancer at the subclonal and single-cell level and in cells responsible for cancer clone maintenance and propagation in childhood acute lymphoblastic leukemia (ALL; see 613065) in which the ETV6/RUNX1 (151385) gene fusion is an early or initiating genetic lesion followed by a modest number of recurrent or driver copy number alterations. By multiplexing fluorescence in situ hybridization probes for these mutations, up to 8 genetic abnormalities could be detected in single cells, a genetic signature of subclones identified, and a composite picture of subclonal architecture and putative ancestral trees assembled. Anderson et al. (2011) observed that subclones in acute lymphoblastic leukemia have variegated genetics and complex nonlinear or branching evolutionary histories. Copy number alterations are independently and reiteratively acquired in subclones of individual patients, and in no preferential order. Clonal architecture is dynamic and is subject to change in the lead-up to a diagnosis and in relapse. Leukemia-propagating cells, assayed by serial transplantation in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) IL2R-gamma (308380)-null mice, are also genetically variegated, mirroring subclonal patterns, and vary in competitive regenerative capacity in vivo. </p><p>The ETV6/RUNX1 fusion gene, found in 25% of childhood ALL cases, is acquired in utero but requires additional somatic mutations for overt leukemia. Papaemmanuil et al. (2014) used exome and low-coverage whole-genome sequencing to characterize secondary events associated with leukemic transformation. RAG (see 179615)-mediated deletions emerged as the dominant mutational process, characterized by recombination signal sequence motifs near breakpoints, incorporation of nontemplated sequence at junctions, approximately 30-fold enrichment at promoters and enhancers of genes actively transcribed in B-cell development, and an unexpectedly high ratio of recurrent to nonrecurrent structural variants. Single-cell tracking showed that this mechanism is active throughout leukemic evolution, with evidence of localized clustering and reiterated deletions. Integration of data on point mutations and rearrangements identified ATF7IP (613644) and MGA (616061) as tumor-suppressor genes in ALL. Papaemmanuil et al. (2014) concluded that a remarkably parsimonious mutational process transforms ETV6/RUNX1-positive lymphoblasts, targeting the promoters, enhancers, and first exons of genes that normally regulate B-cell differentiation. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cytogenetics</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>Cytogenetic abnormalities involving the short arm of chromosome 12 have been documented in a wide variety of hematopoietic malignancies, including acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia, and myelodysplastic syndromes. Among 20 patients with 12q deletions or translocations, Kobayashi et al. (1994) showed that most changes were clustered within a 1.39-Mb region, suggesting that a single gene on 12p13 was affected in these leukemias. </p><p>Raynaud et al. (1996) reported 5 patients with an identical reciprocal translocation between 3q26 and 12p13. This nonrandom cytogenetic change was observed in 4 patients with myelodysplastic syndrome rapidly progressing to acute myeloid leukemia and was found at blast crisis of 1 patient with Philadelphia chromosome-positive CML. The abnormality was associated with a very poor prognosis. Fluorescence in situ hybridization with 3q26 and 12p13 probes was performed on metaphases from these 5 patients. The results were consistent with scattering of the breakpoints previously described in 3q26 rearrangements. Breakpoints at 12p13 involved the ETV6 gene in 3 myelodysplastic syndrome cases. </p><p>Berger et al. (1997) described 3 novel translocations involving the TEL/ETV6 gene on chromosome 12: t(X;12)(q28;p13), t(1;12)(q21;p13), and t(9;12)(p23-24;p13). </p><p>Cave et al. (1997) demonstrated that ETV6 is a target of chromosome 12p deletions in t(12;21) childhood acute lymphocytic leukemia. </p><p>Odero et al. (2001) stated that 35 different chromosome bands had been involved in ETV6 translocations, of which 13 had been cloned. Adding further data, they concluded that ETV6 is involved in 41 translocations. </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><strong><em>Thrombocytopenia 5</em></strong></p><p>
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In affected members of 3 unrelated families with autosomal dominant thrombocytopenia-5 (THC5; 616216) and increased susceptibility to hematopoietic malignancies, Zhang et al. (2015) identified 3 different missense mutations in the ETV6 gene (600618.0003-600618.0005). The mutation in the first family was found by whole-exome sequencing. Functional studies showed that the mutations abrogated DNA binding, altered subcellular localization of ETV6, decreased transcriptional repression in a dominant-negative fashion, and impaired hematopoiesis. These findings identified a central role for ETV6 in hematopoiesis and malignant transformation. </p><p>In affected members of 3 unrelated families with THC5, Noetzli et al. (2015) identified 2 different heterozygous mutations in the ETV6 gene (P214L, 600618.0005 and R418G, 600618.0006). The mutation in the first family was found by whole-exome sequencing; the mutations in the 2 subsequent families were found by direct sequencing of the ETV6 gene in 23 families with a similar phenotype. Functional studies showed that all mutations resulted in decreased transcriptional repression, impaired megakaryocyte maturation, and aberrant cellular localization of mutant and wildtype ETV6, consistent with a dominant-negative effect. </p><p><strong><em>Somatic Mutations</em></strong></p><p>
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Barjesteh van Waalwijk van Doorn-Khosrovani et al. (2005) analyzed 300 patients newly diagnosed with acute myeloid leukemia (AML; 601626) for mutations in the coding region of the ETV6 gene and identified 5 somatic heterozygous mutations affecting either the homodimerization or the DNA-binding domain (e.g., 600618.0001 and 600618.0002). These ETV6 mutant proteins were unable to repress transcription and showed dominant-negative effects. The authors also examined ETV6 protein expression in 77 patients with AML and found that 24 (31%) lacked the wildtype 57- and 50-kD proteins; there was no correlation between ETV6 mRNA transcript levels and the loss of ETV6 protein, suggesting posttranscriptional regulation of ETV6. </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>History</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><strong><em>ETV6/ABL1 Fusion Gene</em></strong></p><p>
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Papadopoulos et al. (1995) identified a case of ALL with a previously undescribed fusion between the TEL gene and the ABL gene (189980) on chromosome 9q. The fusion protein showed elevated tyrosine kinase activity. However, Janssen et al. (1995) did not identify any TEL/ABL fusion products using RT-PCR to screen 186 adult ALL and 30 childhood ALL patients. Nilsson et al. (1998) also found no instance of ETV6/ABL fusion. in a study of a group of 67 cases of chronic myeloid disorders. </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>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By gene targeting in mice, Wang et al. (1997) showed that Tel function is required for viability of the developing mouse. The Tel -/- mice suffered a yolk sac angiogenic defect; Tel also appeared essential for the survival of selected neural and mesenchymal populations within the embryo proper. Wang et al. (1998) generated mouse chimeras with Tel -/- embryonic stem cells to examine a possible requirement in adult hematopoiesis. They found that although Tel function is not required for the intrinsic proliferation and/or differentiation of adult-type hematopoietic lineages in the yolk sac and fetal liver, it is essential for the establishment of hematopoiesis of all lineages in the bone marrow. These findings established TEL as the first transcription factor required specifically for hematopoiesis within the bone marrow, as opposed to other sites of hematopoietic activity during development. </p><p>STAT5 (see STAT5A, 601511; STAT5B, 604260) is activated in a broad spectrum of human hematologic malignancies. Using a genetic approach, Schwaller et al. (2000) addressed whether activation of STAT5 is necessary for the myelo- and lymphoproliferative disease induced by the TEL/JAK2 (147796) fusion gene. Whereas mice transplanted with bone marrow transduced with retrovirus expressing TEL/JAK2 developed a rapidly fatal myelo- and lymphoproliferative syndrome, reconstitution with bone marrow derived from Stat5a/b-deficient mice expressing TEL/JAK2 did not induce disease. Disease induction in the Stat5a/b-deficient background was rescued with a bicistronic retrovirus encoding TEL/JAK2 and Stat5a. Furthermore, myeloproliferative disease was induced by reconstitution with bone marrow cells expressing a constitutively active mutant, Stat5a, or a single Stat5a target, murine oncostatin M (OSM; 165095). These data defined a critical role for STAT5A/B and OSM in the pathogenesis of TEL/JAK2 disease. </p><p>Montpetit and Sinnett (2001) reported a comparative analysis of the ETV6 gene in vertebrate genomes. They cloned the homolog of ETV6 from the compact genome of the pufferfish Fugu rubripes. In that organism the gene, composed of 8 exons, spans about 15 kb and is 16 times smaller than its human counterpart, mainly because of reduced intron size. Three of the 7 introns were unusually large (more than 2 kb). As expected, the PNT and ETS domains were highly conserved from Fugu to human. There were also conserved putative regulatory elements in the promoter as well as in the large intron 2 of Fugu ETV6. </p><p>Creation of the TEL/AML1 fusion disrupts 1 copy of the TEL gene and 1 copy of the AML1 gene; loss of one or the other is associated with cases of acute leukemia without the presence of the TEL/AML1 fusion gene. To determine if TEL/AML1 can contribute to leukemogenesis, Bernardin et al. (2002) transduced marrow from C57BL/6 mice with a retroviral vector expressing TEL/AML1 or with a control vector. Two of the 9 TEL/AML1 mice developed ALL, whereas none of the 20 control mice developed leukemia. Bernardin et al. (2002) also used the TEL/AML1 vector to transduce marrow from C57BL/6 mice lacking the overlapping p16(INK4a)p19(ARF) genes (600160) and transplanted the cells into wildtype recipients. No control mice died, but 6 of 8 TEL/AML1/p16p19 mice died with leukemia. These findings indicated that TEL/AML1 contributes to leukemogenesis and may cooperate with loss of p16p19 to transform lymphoid progenitors. </p><p>Tsuzuki et al. (2004) analyzed hemopoiesis in mice syngeneically transplanted with TEL/AML1-transduced bone marrow stem cells. TEL/AML1 expression was associated with an accumulation/expansion of primitive Kit (164920)-positive multipotent progenitors and a modest increase in myeloid colony-forming cells. TEL/AML1 expression was, however, permissive for myeloid differentiation. Analysis of B lymphopoiesis revealed an increase in early pro-B cells but a differentiation deficit beyond that stage, which resulted in lower B-cell production in the marrow. TEL/AML1-positive B-cell progenitors exhibited reduced expression of genes crucial for the pro-B to pre-B cell transition. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 Selected Examples):</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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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 LEUKEMIA, ACUTE MYELOID, SOMATIC</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ETV6, GLU76TER
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<br />
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SNP: rs121434637,
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ClinVar: RCV000009547
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In leukemic blast cells of a patient with acute myeloid leukemia (601626), Barjesteh van Waalwijk van Doorn-Khosrovani et al. (2005) identified a somatic heterozygous 500G-T transversion in the ETV6 gene, resulting in a glu76-to-ter (E76X) substitution in the N-terminal pointed (PNT) homodimerization domain. The mutant protein was unable to repress transcription and showed dominant-negative effects. The mutation was not found in nonhematopoietic tissue from this patient. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 LEUKEMIA, ACUTE MYELOID, SOMATIC</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ETV6, 3-BP INS, 1307GGG
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<br />
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SNP: rs587776710,
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ClinVar: RCV000009548
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In leukemic blast cells of a patient with acute myeloid leukemia (601626), Barjesteh van Waalwijk van Doorn-Khosrovani et al. (2005) identified a somatic heterozygous 3-bp insertion (1307insGGG) in the ETV6 gene, resulting in the insertion of a glycine between codons 344 and 345 in the DNA binding domain. The mutant protein was unable to repress transcription and showed dominant-negative effects. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 THROMBOCYTOPENIA 5</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ETV6, ARG399CYS
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<br />
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SNP: rs724159945,
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gnomAD: rs724159945,
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ClinVar: RCV000149802, RCV000157609, RCV001824288
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a woman and her 3 children with thrombocytopenia-5 (THC5; 616216), Zhang et al. (2015) identified a heterozygous c.1195C-T transition in the ETV6 gene, resulting in an arg399-to-cys (R399C) substitution at a highly conserved residue in the third alpha-helix of the ETS DNA-binding domain; R399 directly contacts DNA via hydrogen bonds. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the phenotype in the family and was not present in the dbSNP (build 139), 1000 Genomes Project, or Exome Variant Server databases. In vitro electrophoretic studies indicated that the mutation abrogated DNA binding, and functional studies showed that it lost normal transcriptional repression activity in a dominant-negative manner by interfering with homooligomerization. The mutant protein also showed reduced nuclear localization compared to wildtype and impaired hematopoiesis. The family was of German and Native American ancestry; 3 mutation carriers developed hematologic malignancies. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0004 THROMBOCYTOPENIA 5</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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ETV6, ARG369GLN
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<br />
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SNP: rs724159946,
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ClinVar: RCV000149803, RCV000157610, RCV003162607, RCV003372620, RCV003415987
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In 5 affected members of a family of Scottish descent with THC5 (616216), Zhang et al. (2015) identified a heterozygous c.1106G-A transition in the ETV6 gene, resulting in an arg369-to-gln (R369Q) substitution at a highly conserved residue in the second beta-sheet of the ETS DNA-binding domain. The mutation was not present in the dbSNP (build 139), 1000 Genomes Project, or Exome Variant Server databases. In vitro electrophoretic studies indicated that the mutation abrogated DNA binding, and functional studies showed that it lost normal transcriptional repression activity in a dominant-negative manner by interfering with homo-oligomerization. The mutant protein also showed reduced nuclear localization compared to wildtype and impaired hematopoiesis. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 THROMBOCYTOPENIA 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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ETV6, PRO214LEU
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<br />
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SNP: rs724159947,
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ClinVar: RCV000149804, RCV000157611, RCV001281572, RCV001818340
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In an African American woman with thrombocytopenia-5 (THC5; 616216) who developed mixed T-cell/myeloid acute leukemia, Zhang et al. (2015) identified a heterozygous c.641C-T transition in the ETV6 gene, resulting in a pro214-to-leu (P214L) substitution at a highly conserved residue in a linker inhibitory domain that indirectly promotes DNA binding. The mutation was not present in the dbSNP (build 139), 1000 Genomes Project, or Exome Variant Server databases. Expression of the mutation in HeLa cells showed that the mutant protein had predominantly cytoplasmic localization, rather than normal nuclear localization. The mutant protein also impaired hematopoiesis. </p><p>In affected members of a family with THC5, Noetzli et al. (2015) identified heterozygosity for the c.641C-T transition (c.641C-T, NM_001987) in the ETV6 gene, resulting in a P214L substitution. The mutation was found by whole-exome sequencing and segregated with the disorder in the family. Direct screening of the ETV6 gene in 23 additional families with autosomal dominant thrombocytopenia identified 1 family with the same P214L mutation. Three patients from the 2 families developed B-cell leukemia. In vitro functional expression studies showed that the P214L mutant protein had less transcriptional repression activity than wildtype. Transfection of the mutation into CD34+ cells cultured with thrombopoietin resulted in delayed and decreased megakaryocyte maturation compared to control cells. There was aberrant cytoplasmic localization of both the mutant and wildtype protein, consistent with a dominant-negative effect. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 THROMBOCYTOPENIA 5</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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|
<span class="mim-text-font">
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ETV6, ARG418GLY
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<br />
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SNP: rs786205226,
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|
|
ClinVar: RCV000170497, RCV004020022
|
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|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with autosomal dominant thrombocytopenia-5 (THC5; 616216), Noetzli et al. (2015) identified a heterozygous c.1252A-G transition (c.1252A-G, NM_001987) in the last codon of exon 7 of the ETV6 gene, predicted to result in an arg418-to-gly (R418G) substitution at a highly conserved residue in the DNA-binding domain. Analysis of patient cells showed that the mutation also disrupted a splice site, resulting in an alternatively spliced product with the skipping of exon 7, a partial deletion of the putative DNA-binding domain (385_418del), and a subsequent frameshift and premature termination (Asn385ValfsTer7). The truncated protein was expressed in transfected HEK293T cells, but not in patient platelets. The mutation was not found in the 1000 Genomes Project database. In vitro functional expression studies showed that both the R418G mutant protein and the truncated protein had less transcriptional repression activity than wildtype. Transfection of the R418G mutation into CD34+ cells cultured with thrombopoietin resulted in delayed and decreased megakaryocyte maturation compared to control cells. There was aberrant cytoplasmic localization of both the mutant and wildtype protein, consistent with a dominant-negative effect. </p>
|
|
</span>
|
|
</div>
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|
<div>
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|
<br />
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</div>
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|
</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
|
<ol>
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<li>
|
|
<p class="mim-text-font">
|
|
Anderson, K., Lutz, C., van Delft, F. W., Bateman, C. M., Guo, Y., Colman, S. M., Kempski, H., Moorman, A. V., Titley, I., Swansbury, J., Kearney, L., Enver, T., Greaves, M.
|
|
<strong>Genetic variegation of clonal architecture and propagating cells in leukaemia.</strong>
|
|
Nature 469: 356-361, 2011.
|
|
|
|
|
|
[PubMed: 21160474]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09650]
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</p>
|
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</li>
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|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Apperley, J. F., Gardembas, M., Melo, J. V., Russell-Jones, R., Bain, B. J., Baxter, E. J., Chase, A., Chessells, J. M., Colombat, M., Dearden, C. E., Dimitrijevic, S., Mahon, F.-X., Marin, D., Nikolova, Z., Olavarria, E., Silberman, S., Schultheis, B., Cross, N. C. P., Goldman, J. M.
|
|
<strong>Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta.</strong>
|
|
New Eng. J. Med. 347: 481-487, 2002.
|
|
|
|
|
|
[PubMed: 12181402]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa020150]
|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Baens, M., Peeters, P., Guo, C., Aerssens, J., Marynen, P.
|
|
<strong>Genomic organization of TEL: the human ETS-variant gene 6.</strong>
|
|
Genome Res. 6: 404-413, 1996.
|
|
|
|
|
|
[PubMed: 8743990]
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|
|
|
|
|
[Full Text: https://doi.org/10.1101/gr.6.5.404]
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Barjesteh van Waalwijk van Doorn-Khosrovani, S., Spensberger, D., de Knegt, Y., Tang, M., Lowenberg, B., Delwel, R.
|
|
<strong>Somatic heterozygous mutations in ETV6 (TEL) and frequent absence of ETV6 protein in acute myeloid leukemia.</strong>
|
|
Oncogene 24: 4129-4137, 2005.
|
|
|
|
|
|
[PubMed: 15806161]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.onc.1208588]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berger, R., Le Coniat, M., Lacronique, V., Daniel, M.-T., Lessard, M., Berthou, C., Marynen, P., Bernard, O.
|
|
<strong>Chromosome abnormalities of the short arm of chromosome 12 in hematopoietic malignancies: a report including three novel translocations involving the TEL/ETV6 gene.</strong>
|
|
Leukemia 11: 1400-1403, 1997.
|
|
|
|
|
|
[PubMed: 9305591]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.leu.2400785]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bernardin, F., Yang, Y., Cleaves, R., Zahurak, M., Cheng, L., Civin, C. I., Friedman, A. D.
|
|
<strong>TEL-AML1, expressed from t(12;21) in human acute lymphocytic leukemia, induces acute leukemia in mice.</strong>
|
|
Cancer Res. 62: 3904-3908, 2002.
|
|
|
|
|
|
[PubMed: 12124316]
|
|
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Buijs, A., Sherr, S., van Baal, S., van Bezouw, S., van der Plas, D., Geurts van Kessel, A., Riegman, P., Lekanne Deprez, R., Zwarthoff, E., Hagemeijer, A., Grosveld, G.
|
|
<strong>Translocation (12;22)(p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12q13 to the MN1 gene on 22q11.</strong>
|
|
Oncogene 10: 1511-1519, 1995. Note: Erratum: Oncogene 11: 809 only, 1995.
|
|
|
|
|
|
[PubMed: 7731705]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cave, H., Cacheux, V., Raynaud, S., Brunie, G., Bakkus, M., Cochaux, P., Preudhomme, C., Lai, J. L., Vilmer, E., Grandchamp, B.
|
|
<strong>ETV6 is the target of chromosome 12p deletions in t(12;21) childhood acute lymphocytic leukemia.</strong>
|
|
Leukemia 11: 1459-1464, 1997.
|
|
|
|
|
|
[PubMed: 9305598]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.leu.2400798]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cazzaniga, G., Tosi, S., Aloisi, A., Giudici, G., Daniotti, M., Pioltelli, P., Kearney, L., Biondi, A.
|
|
<strong>The tyrosine kinase Abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts.</strong>
|
|
Blood 94: 4370-4373, 1999.
|
|
|
|
|
|
[PubMed: 10590083]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cools, J., Bilhou-Nabera, C., Wlodarska, I., Cabrol, C., Talmant, P., Bernard, P., Hagemeijer, A., Marynen, P.
|
|
<strong>Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13).</strong>
|
|
Blood 94: 1820-1824, 1999.
|
|
|
|
|
|
[PubMed: 10477709]
|
|
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ford, A. M., Bennett, C. A., Price, C. M., Bruin, M. C. A., Van Wering, E. R., Greaves, M.
|
|
<strong>Fetal origins of the TEL-AML1 fusion gene in identical twins with leukemia.</strong>
|
|
Proc. Nat. Acad. Sci. 95: 4584-4588, 1998.
|
|
|
|
|
|
[PubMed: 9539781]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.95.8.4584]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Golub, T. R., Barker, G. F., Bohlander, S. K., Hiebert, S. W., Ward, D. C., Bray-Ward, P., Morgan, E., Raimondi, S. C., Rowley, J. D., Gilliland, D. G.
|
|
<strong>Fusion of the TEL gene on 12p13 to the AML1 gene on 21q22 in acute lymphoblastic leukemia.</strong>
|
|
Proc. Nat. Acad. Sci. 92: 4917-4921, 1995.
|
|
|
|
|
|
[PubMed: 7761424]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.92.11.4917]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Golub, T. R., Barker, G. F., Lovett, M., Gilliland, D. G.
|
|
<strong>Fusion of PDGF receptor beta to a novel ets-like gene, tel, in chronic myelomonocytic leukemia with t(5;12) chromosomal translocation.</strong>
|
|
Cell 77: 307-316, 1994.
|
|
|
|
|
|
[PubMed: 8168137]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0092-8674(94)90322-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Janssen, J. W. G., Ridge, S. A., Papadopoulos, P., Cotter, F., Ludwig, W.-D., Fonatsch, C., Rieder, H., Ostertag, W., Bartram, C. R., Wiedemann, L. M.
|
|
<strong>The fusion of TEL and ABL in human acute lymphoblastic leukaemia is a rare event.</strong>
|
|
Brit. J. Haemat. 90: 222-224, 1995.
|
|
|
|
|
|
[PubMed: 7786792]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.1995.tb03407.x]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Knezevich, S. R., McFadden, D. E., Tao, W., Lim, J. F., Sorensen, P. H. B.
|
|
<strong>A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma.</strong>
|
|
Nature Genet. 18: 184-187, 1998.
|
|
|
|
|
|
[PubMed: 9462753]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0298-184]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kobayashi, H., Montgomery, K. T., Bohlander, S. K., Adra, C. N., Lim, B. L., Kucherlapati, R. S., Donis-Keller, H., Holt, M. S., Le Beau, M. M., Rowley, J. D.
|
|
<strong>Fluorescence in situ hybridization mapping of translocations and deletions involving the short arm of human chromosome 12 in malignant hematologic diseases.</strong>
|
|
Blood 84: 3473-3482, 1994.
|
|
|
|
|
|
[PubMed: 7949101]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lacronique, V., Boureux, A., Della Valle, V., Poirel, H., Quang, C. T., Mauchauffe, M., Berthou, C., Lessard, M., Berger, R., Ghysdael, J., Bernard, O. A.
|
|
<strong>A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia.</strong>
|
|
Science 278: 1309-1312, 1997.
|
|
|
|
|
|
[PubMed: 9360930]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.278.5341.1309]
|
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|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Montpetit, A., Sinnett, D.
|
|
<strong>Comparative analysis of the ETV6 gene in vertebrate genomes from pufferfish to human.</strong>
|
|
Oncogene 20: 3437-3442, 2001.
|
|
|
|
|
|
[PubMed: 11423994]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.onc.1204444]
|
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|
|
</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Nilsson, T., Andreasson, P., Hoglund, M., Fioretos, T., Billstrom, R., Garwicz, S., Mitelman, F., Johansson, B.
|
|
<strong>ETV6/ABL fusion is rare in Ph-negative chronic myeloid disorders.</strong>
|
|
Leukemia 12: 1167-1168, 1998.
|
|
|
|
|
|
[PubMed: 9665207]
|
|
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|
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[Full Text: https://doi.org/10.1038/sj.leu.2401091]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Noetzli, L., Lo, R. W., Lee-Sherick, A. B., Callaghan, M., Noris, P., Savoia, A., Rajpurkar, M., Jones, K., Gowan, K., Balduini, C. L., Pecci, A., Gnan, C., and 16 others.
|
|
<strong>Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia.</strong>
|
|
Nature Genet. 47: 535-538, 2015.
|
|
|
|
|
|
[PubMed: 25807284]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.3253]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Odero, M. D., Carlson, K., Calasanz, M. J., Lahortiga, I., Chinwalla, V., Rowley, J. D.
|
|
<strong>Identification of new translocations involving ETV6 in hematologic malignancies by fluorescence in situ hybridization and spectral karyotyping.</strong>
|
|
Genes Chromosomes Cancer 31: 134-142, 2001.
|
|
|
|
|
|
[PubMed: 11319801]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/gcc.1127]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Odero, M. D., Vizmanos, J. L., Roman, J. P., Lahortiga, I., Panizo, C., Calasanz, M. J., Zeleznik-Le, N. J., Rowley, J. D., Novo, F. J.
|
|
<strong>A novel gene, MDS2, is fused to ETV6/TEL in a t(1;12)(p36.1;p13) in a patient with myelodysplastic syndrome.</strong>
|
|
Genes Chromosomes Cancer 35: 11-19, 2002.
|
|
|
|
|
|
[PubMed: 12203785]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/gcc.10090]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Papadopoulos, P., Ridge, S. A., Boucher, C. A., Stocking, C., Wiedemann, L. M.
|
|
<strong>The novel activation of ABL by fusion to an ets-related gene, TEL.</strong>
|
|
Cancer Res. 55: 34-38, 1995.
|
|
|
|
|
|
[PubMed: 7805037]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Papaemmanuil, E., Rapado, I., Li, Y., Potter, N. E., Wedge, D. C., Tubio, J., Alexandrov, L. B., Van Loo, P., Cooke, S. L., Marshall, J., Martincorena, I., Hinton, J., and 25 others.
|
|
<strong>RAG-mediated recombination is the predominant driver of oncogenic rearrangement in ETV6-RUNX1 acute lymphoblastic leukemia.</strong>
|
|
Nature Genet. 46: 116-125, 2014.
|
|
|
|
|
|
[PubMed: 24413735]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.2874]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Peeters, P., Raynaud, S. D., Cools, J., Wlodarska, I., Grosgeorge, J., Philip, P., Monpoux, F., Van Rompaey, L., Baens, M., Van den Berghe, H., Marynen, P.
|
|
<strong>Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia.</strong>
|
|
Blood 90: 2535-2540, 1997.
|
|
|
|
|
|
[PubMed: 9326218]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Penas, E. M. M., Cools, J., Algenstaedt, P., Hinz, K., Seeger, D., Schafhausen, P., Schilling, G., Marynen, P., Hossfeld, D. K., Dierlamm, J.
|
|
<strong>A novel cryptic translocation t(12;17)(p13;p12-p13) in a secondary acute myeloid leukemia results in a fusion of the ETV6 gene and the antisense strand of the PER1 gene.</strong>
|
|
Genes Chromosomes Cancer 37: 79-83, 2003.
|
|
|
|
|
|
[PubMed: 12661008]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/gcc.10175]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pierce, A., Carney, L., Hamza, H. G., Griffiths, J. R., Zhang, L., Whetton, B. A., Gonzalez Sanchez, M. B., Tamura, T., Sternberg, D., Whetton, A. D.
|
|
<strong>THOC5 spliceosome protein: a target for leukaemogenic tyrosine kinases that affects inositol lipid turnover.</strong>
|
|
Brit. J. Haemat. 141: 641-650, 2008.
|
|
|
|
|
|
[PubMed: 18373705]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1111/j.1365-2141.2008.07090.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Raynaud, S. D., Baens, M., Grosgeorge, J., Rodgers, K., Reid, C. D. L., Dainton, M., Dyer, M., Fuzibet, J. G., Gratecos, N., Taillan, B., Ayraud, N., Marynen, P.
|
|
<strong>Fluorescence in situ hybridization analysis of t(3;12)(q26;p13): a recurring chromosomal abnormality involving the TEL gene (ETV6) in myelodysplastic syndromes.</strong>
|
|
Blood 88: 682-689, 1996.
|
|
|
|
|
|
[PubMed: 8695816]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Romana, S. P., Poirel, H., Leconiat, M., Flexor, M.-A., Mauchauffe, M., Jonveaux, P., Macintyre, E. A., Berger, R., Bernard, O. A.
|
|
<strong>High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia.</strong>
|
|
Blood 86: 4263-4269, 1995.
|
|
|
|
|
|
[PubMed: 7492786]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Salomon-Nguyen, F., Della-Valle, V., Mauchauffe, M., Busson-Le Coniat, M., Ghysdael, J., Berger, R., Bernard, O. A.
|
|
<strong>The t(1;12)(q21;p13) translocation of human acute myeloblastic leukemia results in a TEL-ARNT fusion.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 6757-6762, 2000.
|
|
|
|
|
|
[PubMed: 10829078]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.120162297]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Schwaller, J., Parganas, E., Wang, D., Cain, D., Aster, J. C., Williams, I. R., Lee, C.-K., Gerthner, R., Kitamura, T., Frantsve, J., Anastasiadou, E., Loh, M. L., Levy, D. E., Ihle, J. N., Gilliland, D. G.
|
|
<strong>Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2.</strong>
|
|
Molec. Cell 6: 693-704, 2000.
|
|
|
|
|
|
[PubMed: 11030348]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1097-2765(00)00067-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Stegmaier, K., Pendse, S., Barker, G. F., Bray-Ward, P., Ward, D. C., Montgomery, K. T., Krauter, K. S., Reynolds, C., Sklar, J., Donnelly, M., Bohlander, S. K., Rowley, J. D., Sallan, S. E., Gilliland, D. G., Golub, T. R.
|
|
<strong>Frequent loss of heterozygosity at the TEL gene locus in acute lymphoblastic leukemia of childhood.</strong>
|
|
Blood 86: 38-44, 1995.
|
|
|
|
|
|
[PubMed: 7795247]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Tsuzuki, S., Seto, M., Greaves, M., Enver, T.
|
|
<strong>Modeling first-hit functions of the t(12;21) TEL-AML1 translocation in mice.</strong>
|
|
Proc. Nat. Acad. Sci. 101: 8443-8448, 2004.
|
|
|
|
|
|
[PubMed: 15155899]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0402063101]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, L. C., Kuo, F., Fujiwara, Y., Gilliland, D. G., Golub, T. R., Orkin, S. H.
|
|
<strong>Yolk sac angiogenic defect and intra-embryonic apoptosis in mice lacking the Ets-related factor TEL.</strong>
|
|
EMBO J. 16: 4374-4383, 1997.
|
|
|
|
|
|
[PubMed: 9250681]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/emboj/16.14.4374]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, L. C., Swat, W., Fujiwara, Y., Davdison, L., Visvader, J., Kuo, F., Alt, F. W., Gilliland, D. G., Golub, T. R., Orkin, S. H.
|
|
<strong>The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow.</strong>
|
|
Genes Dev. 12: 2392-2401, 1998.
|
|
|
|
|
|
[PubMed: 9694803]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.12.15.2392]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yagasaki, F., Jinnai, I., Yoshida, S., Yokoyama, Y., Matsuda, A., Kusumoto, S., Kobayashi, H., Terasaki, H., Ohyashiki, K., Asou, N., Murohashi, I., Bessho, M., Hirashima, K.
|
|
<strong>Fusion of TEL/ETV6 to a novel ACS2 in myelodysplastic syndrome and acute myelogenous leukemia with t(5;12)(q31;p13).</strong>
|
|
Genes Chromosomes Cancer 26: 192-202, 1999.
|
|
|
|
|
|
[PubMed: 10502316]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1098-2264(199911)26:3<192::aid-gcc2>3.0.co;2-e]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Zhang, M. Y., Churpek, J. E., Keel, S. B., Walsh, T., Lee, M. K., Loeb, K. R., Gulsuner, S., Pritchard, C. C., Sanchez-Bonilla, M., Delrow, J. L., Basom, R. S., Forouhar, M., and 14 others.
|
|
<strong>Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy.</strong>
|
|
Nature Genet. 47: 180-185, 2015.
|
|
|
|
|
|
[PubMed: 25581430]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.3177]
|
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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