3848 lines
374 KiB
Text
3848 lines
374 KiB
Text
|
|
|
|
|
|
|
|
|
|
<!DOCTYPE html>
|
|
<html xmlns="http://www.w3.org/1999/xhtml" lang="en-us" xml:lang="en-us" >
|
|
|
|
<head>
|
|
|
|
|
|
|
|
<!--
|
|
################################# CRAWLER WARNING #################################
|
|
|
|
- The terms of service and the robots.txt file disallows crawling of this site,
|
|
please see https://omim.org/help/agreement for more information.
|
|
|
|
- A number of data files are available for download at https://omim.org/downloads.
|
|
|
|
- We have an API which you can learn about at https://omim.org/help/api and register
|
|
for at https://omim.org/api, this provides access to the data in JSON & XML formats.
|
|
|
|
- You should feel free to contact us at https://omim.org/contact to figure out the best
|
|
approach to getting the data you need for your work.
|
|
|
|
- WE WILL AUTOMATICALLY BLOCK YOUR IP ADDRESS IF YOU CRAWL THIS SITE.
|
|
|
|
- WE WILL ALSO AUTOMATICALLY BLOCK SUB-DOMAINS AND ADDRESS RANGES IMPLICATED IN
|
|
DISTRIBUTED CRAWLS OF THIS SITE.
|
|
|
|
################################# CRAWLER WARNING #################################
|
|
-->
|
|
|
|
|
|
|
|
<meta http-equiv="content-type" content="text/html; charset=utf-8" />
|
|
<meta http-equiv="cache-control" content="no-cache" />
|
|
<meta http-equiv="pragma" content="no-cache" />
|
|
<meta name="robots" content="index, follow" />
|
|
|
|
|
|
<meta name="viewport" content="width=device-width, initial-scale=1" />
|
|
<meta http-equiv="X-UA-Compatible" content="IE=edge" />
|
|
|
|
|
|
<meta name="title" content="Online Mendelian Inheritance in Man (OMIM)" />
|
|
<meta name="description" content="Online Mendelian Inheritance in Man (OMIM) is a comprehensive, authoritative
|
|
compendium of human genes and genetic phenotypes that is freely available and updated daily. The full-text,
|
|
referenced overviews in OMIM contain information on all known mendelian disorders and over 15,000 genes.
|
|
OMIM focuses on the relationship between phenotype and genotype. It is updated daily, and the entries
|
|
contain copious links to other genetics resources." />
|
|
<meta name="keywords" content="Mendelian Inheritance in Man, OMIM, Mendelian diseases, Mendelian disorders, genetic diseases,
|
|
genetic disorders, genetic disorders in humans, genetic phenotypes, phenotype and genotype, disease models, alleles,
|
|
genes, dna, genetics, dna testing, gene testing, clinical synopsis, medical genetics" />
|
|
<meta name="theme-color" content="#333333" />
|
|
<link rel="icon" href="/static/omim/favicon.png" />
|
|
<link rel="apple-touch-icon" href="/static/omim/favicon.png" />
|
|
<link rel="manifest" href="/static/omim/manifest.json" />
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script id='mimBrowserCapability'>
|
|
function _0x5069(){const _0x4b1387=['91sZIeLc','mimBrowserCapability','15627zshTnf','710004yxXedd','34LxqNYj','match','disconnect','1755955rnzTod','observe','1206216ZRfBWB','575728fqgsYy','webdriver','documentElement','close','open','3086704utbakv','7984143PpiTpt'];_0x5069=function(){return _0x4b1387;};return _0x5069();}function _0xe429(_0x472ead,_0x43eb70){const _0x506916=_0x5069();return _0xe429=function(_0xe42949,_0x1aaefc){_0xe42949=_0xe42949-0x1a9;let _0xe6add8=_0x506916[_0xe42949];return _0xe6add8;},_0xe429(_0x472ead,_0x43eb70);}(function(_0x337daa,_0x401915){const _0x293f03=_0xe429,_0x5811dd=_0x337daa();while(!![]){try{const _0x3dc3a3=parseInt(_0x293f03(0x1b4))/0x1*(-parseInt(_0x293f03(0x1b6))/0x2)+parseInt(_0x293f03(0x1b5))/0x3+parseInt(_0x293f03(0x1b0))/0x4+-parseInt(_0x293f03(0x1b9))/0x5+parseInt(_0x293f03(0x1aa))/0x6+-parseInt(_0x293f03(0x1b2))/0x7*(parseInt(_0x293f03(0x1ab))/0x8)+parseInt(_0x293f03(0x1b1))/0x9;if(_0x3dc3a3===_0x401915)break;else _0x5811dd['push'](_0x5811dd['shift']());}catch(_0x4dd27b){_0x5811dd['push'](_0x5811dd['shift']());}}}(_0x5069,0x84d63),(function(){const _0x9e4c5f=_0xe429,_0x363a26=new MutationObserver(function(){const _0x458b09=_0xe429;if(document!==null){let _0x2f0621=![];navigator[_0x458b09(0x1ac)]!==![]&&(_0x2f0621=!![]);for(const _0x427dda in window){_0x427dda[_0x458b09(0x1b7)](/cdc_[a-z0-9]/ig)&&(_0x2f0621=!![]);}_0x2f0621===!![]?document[_0x458b09(0x1af)]()[_0x458b09(0x1ae)]():(_0x363a26[_0x458b09(0x1b8)](),document['getElementById'](_0x458b09(0x1b3))['remove']());}});_0x363a26[_0x9e4c5f(0x1a9)](document[_0x9e4c5f(0x1ad)],{'childList':!![]});}()));
|
|
</script>
|
|
|
|
|
|
|
|
<link rel='preconnect' href='https://cdn.jsdelivr.net' />
|
|
<link rel='preconnect' href='https://cdnjs.cloudflare.com' />
|
|
|
|
<link rel="preconnect" href="https://www.googletagmanager.com" />
|
|
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery@3.7.1/dist/jquery.min.js" integrity="sha256-/JqT3SQfawRcv/BIHPThkBvs0OEvtFFmqPF/lYI/Cxo=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-migrate@3.5.2/dist/jquery-migrate.js" integrity="sha256-ThFcNr/v1xKVt5cmolJIauUHvtXFOwwqiTP7IbgP8EU=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/js/bootstrap.min.js" integrity="sha256-nuL8/2cJ5NDSSwnKD8VqreErSWHtnEP9E7AySL+1ev4=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap.min.css" integrity="sha256-bZLfwXAP04zRMK2BjiO8iu9pf4FbLqX6zitd+tIvLhE=" crossorigin="anonymous">
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/bootstrap@3.4.1/dist/css/bootstrap-theme.min.css" integrity="sha256-8uHMIn1ru0GS5KO+zf7Zccf8Uw12IA5DrdEcmMuWLFM=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/moment@2.29.4/min/moment.min.js" integrity="sha256-80OqMZoXo/w3LuatWvSCub9qKYyyJlK0qnUCYEghBx8=" crossorigin="anonymous"></script>
|
|
<script src="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/js/bootstrap-datetimepicker.min.js" integrity="sha256-dYxUtecag9x4IaB2vUNM34sEso6rWTgEche5J6ahwEQ=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/eonasdan-bootstrap-datetimepicker@4.17.49/build/css/bootstrap-datetimepicker.min.css" integrity="sha256-9FNpuXEYWYfrusiXLO73oIURKAOVzqzkn69cVqgKMRY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.js" integrity="sha256-a+PRq3NbyK3G08Boio9X6+yFiHpTSIrbE7uzZvqmDac=" crossorigin="anonymous"></script>
|
|
<link rel="stylesheet" href="https://cdn.jsdelivr.net/npm/qtip2@3.0.3/dist/jquery.qtip.min.css" integrity="sha256-JvdVmxv7Q0LsN1EJo2zc1rACwzatOzkyx11YI4aP9PY=" crossorigin="anonymous">
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/devbridge-autocomplete@1.4.11/dist/jquery.autocomplete.min.js" integrity="sha256-BNpu3uLkB3SwY3a2H3Ue7WU69QFdSRlJVBrDTnVKjiA=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/jquery-validation@1.21.0/dist/jquery.validate.min.js" integrity="sha256-umbTaFxP31Fv6O1itpLS/3+v5fOAWDLOUzlmvOGaKV4=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdn.jsdelivr.net/npm/js-cookie@3.0.5/dist/js.cookie.min.js" integrity="sha256-WCzAhd2P6gRJF9Hv3oOOd+hFJi/QJbv+Azn4CGB8gfY=" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
<script src="https://cdnjs.cloudflare.com/ajax/libs/ScrollToFixed/1.0.8/jquery-scrolltofixed-min.js" integrity="sha512-ohXbv1eFvjIHMXG/jY057oHdBZ/jhthP1U3jES/nYyFdc9g6xBpjDjKIacGoPG6hY//xVQeqpWx8tNjexXWdqA==" crossorigin="anonymous"></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script async src="https://www.googletagmanager.com/gtag/js?id=G-HMPSQC23JJ"></script>
|
|
<script>
|
|
window.dataLayer = window.dataLayer || [];
|
|
function gtag(){window.dataLayer.push(arguments);}
|
|
gtag("js", new Date());
|
|
gtag("config", "G-HMPSQC23JJ");
|
|
</script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<script src="/static/omim/js/site.js?version=Zmk5Y1" integrity="sha256-fi9cXywxCO5p0mU1OSWcMp0DTQB4s8ncFR8j+IO840s="></script>
|
|
|
|
|
|
<link rel="stylesheet" href="/static/omim/css/site.css?version=VGE4MF" integrity="sha256-Ta80Qpm3w1S8kmnN0ornbsZxdfA32R42R4ncsbos0YU=" />
|
|
|
|
|
|
<script src="/static/omim/js/entry/entry.js?version=anMvRU" integrity="sha256-js/EBOBZzGDctUqr1VhnNPzEiA7w3HM5JbFmOj2CW84="></script>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimBootstrapDeviceSize">
|
|
<div class="visible-xs" data-mim-bootstrap-device-size="xs"></div>
|
|
<div class="visible-sm" data-mim-bootstrap-device-size="sm"></div>
|
|
<div class="visible-md" data-mim-bootstrap-device-size="md"></div>
|
|
<div class="visible-lg" data-mim-bootstrap-device-size="lg"></div>
|
|
</div>
|
|
|
|
|
|
|
|
<title>
|
|
|
|
Entry
|
|
|
|
- #155255 - MEDULLOBLASTOMA; MDB
|
|
|
|
|
|
- OMIM
|
|
|
|
</title>
|
|
|
|
|
|
|
|
</head>
|
|
|
|
<body>
|
|
<div id="mimBody">
|
|
|
|
|
|
|
|
<div id="mimHeader" class="hidden-print">
|
|
|
|
|
|
|
|
<nav class="navbar navbar-inverse navbar-fixed-top mim-navbar-background">
|
|
<div class="container-fluid">
|
|
|
|
<!-- Brand and toggle get grouped for better mobile display -->
|
|
<div class="navbar-header">
|
|
<button type="button" class="navbar-toggle collapsed" data-toggle="collapse" data-target="#mimNavbarCollapse" aria-expanded="false">
|
|
<span class="sr-only"> Toggle navigation </span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
<span class="icon-bar"></span>
|
|
</button>
|
|
<a class="navbar-brand" href="/"><img alt="OMIM" src="/static/omim/icons/OMIM_davinciman.001.png" height="30" width="30"></a>
|
|
</div>
|
|
|
|
<div id="mimNavbarCollapse" class="collapse navbar-collapse">
|
|
|
|
<ul class="nav navbar-nav">
|
|
|
|
|
|
<li>
|
|
<a href="/help/about"><span class="mim-navbar-menu-font"> About </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimStatisticsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Statistics <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="statisticsDropdown">
|
|
<li>
|
|
<a href="/statistics/update"> Update List </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/entry"> Entry Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/geneMap"> Phenotype-Gene Statistics </a>
|
|
</li>
|
|
<li>
|
|
<a href="/statistics/paceGraph"> Pace of Gene Discovery Graph </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDownloadsDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Downloads <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="downloadsDropdown">
|
|
|
|
<li>
|
|
<a href="/downloads/"> Register for Downloads </a>
|
|
</li>
|
|
<li>
|
|
<a href="/api"> Register for API Access </a>
|
|
</li>
|
|
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="/contact?mimNumber=155255"><span class="mim-navbar-menu-font"> Contact Us </span></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li>
|
|
|
|
<a href="/mimmatch/">
|
|
|
|
<span class="mim-navbar-menu-font">
|
|
<span class="mim-tip-bottom" qtip_title="<strong>MIMmatch</strong>" qtip_text="MIMmatch is a way to follow OMIM entries that interest you and to find other researchers who may share interest in the same entries. <br /><br />A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.">
|
|
MIMmatch
|
|
</span>
|
|
</span>
|
|
</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimDonateDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Donate <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="donateDropdown">
|
|
<li>
|
|
<a href="https://secure.jhu.edu/form/OMIM" target="_blank" onclick="gtag('event', 'mim_donation', {'destination': 'secure.jhu.edu'})"> Donate! </a>
|
|
</li>
|
|
<li>
|
|
<a href="/donors"> Donors </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li class="dropdown">
|
|
<a href="#" id="mimHelpDropdown" class="dropdown-toggle" data-toggle="dropdown" role="button" aria-haspopup="true" aria-expanded="false"><span class="mim-navbar-menu-font"> Help <span class="caret"></span></span></a>
|
|
<ul class="dropdown-menu" role="menu" aria-labelledby="helpDropdown">
|
|
<li>
|
|
<a href="/help/faq"> Frequently Asked Questions (FAQs) </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/search"> Search Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/linking"> Linking Help </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/api"> API Help </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/external"> External Links </a>
|
|
</li>
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/help/agreement"> Use Agreement </a>
|
|
</li>
|
|
<li>
|
|
<a href="/help/copyright"> Copyright </a>
|
|
</li>
|
|
</ul>
|
|
</li>
|
|
|
|
|
|
|
|
<li>
|
|
<a href="#" id="mimShowTips" class="mim-tip-hint" title="Click to reveal all tips on the page. You can also hover over individual elements to reveal the tip."><span class="mim-navbar-menu-font"><span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span></span></a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimSearch" class="hidden-print">
|
|
|
|
<div class="container">
|
|
|
|
<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
|
|
|
|
<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
|
|
<input type="hidden" id="mimSearchStart" name="start" value="1" />
|
|
<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
|
|
<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
|
|
<div class="form-group">
|
|
<div class="input-group">
|
|
<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
|
|
<div class="input-group-btn">
|
|
<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
|
|
<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
|
|
<ul class="dropdown-menu dropdown-menu-right">
|
|
<li class="dropdown-header">
|
|
Advanced Search
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/entry"> OMIM </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
|
|
</li>
|
|
<li style="margin-left: 0.5em;">
|
|
<a href="/search/advanced/geneMap"> Gene Map </a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="separator" class="divider"></li>
|
|
<li>
|
|
<a href="/history"> Search History </a>
|
|
</li>
|
|
|
|
|
|
</ul>
|
|
</div>
|
|
</div>
|
|
<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="col-lg-4 col-md-4 col-sm-4 col-xs-4">
|
|
<span class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</form>
|
|
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
<!-- <div id="mimSearch"> -->
|
|
|
|
|
|
|
|
|
|
<div id="mimContent">
|
|
|
|
|
|
|
|
<div class="container hidden-print">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
|
|
<div id="mimAlertBanner">
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
|
|
<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
|
|
|
|
<div id="mimFloatingTocMenu" class="small" role="navigation">
|
|
|
|
<p>
|
|
<span class="h4">#155255</span>
|
|
<br />
|
|
<strong>Table of Contents</strong>
|
|
</p>
|
|
|
|
<nav>
|
|
<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
|
|
|
|
<li role="presentation">
|
|
<a href="#title"><strong>Title</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="/clinicalSynopsis/155255"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#text"><strong>Text</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#description">Description</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalFeatures">Clinical Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#pathogenesis">Pathogenesis</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#clinicalManagement">Clinical Management</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#mapping">Mapping</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#molecularGenetics">Molecular Genetics</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#references"><strong>References</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#contributors"><strong>Contributors</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#creationDate"><strong>Creation Date</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#editHistory"><strong>Edit History</strong></a>
|
|
</li>
|
|
|
|
</ul>
|
|
|
|
</nav>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<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">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimFloatingLinksMenu">
|
|
|
|
<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
|
<h4 class="panel-title">
|
|
<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
|
|
<div style="display: table-row">
|
|
<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">External Links</div>
|
|
</div>
|
|
</a>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
|
|
<div id="mimExternalLinksFold" class="collapse in">
|
|
|
|
<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
|
|
|
|
<div style="display: table-cell;">Clinical Resources</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://clinicaltrials.gov/search?cond=(MEDULLOBLASTOMA) OR (BRCA2 OR GPR161 OR CTNNB1 OR ELP1 OR PTCH2 OR SUFU)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
|
|
<div id="mimEuroGentestFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=19681&Typ=Pat" title="Medulloblastoma with extensive nodularity" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Medulloblastoma with exten… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=19682&Typ=Pat" title="Desmoplastic/nodular medulloblastoma" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Desmoplastic/nodular medul… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=19683&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Classic medulloblastoma </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=3751&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Medulloblastoma </a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.diseaseinfosearch.org/x/4552" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=155255[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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
|
|
<div id="mimOrphanetFold" class="collapse">
|
|
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251858" title="Medulloblastoma with extensive nodularity" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Medulloblastoma with exten…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251863" title="Desmoplastic/nodular medulloblastoma" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Desmoplastic/nodular medul…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=251867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Classic medulloblastoma</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=616" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Medulloblastoma</a></div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Animal Models</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.alliancegenome.org/disease/DOID:0050902" 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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="http://www.informatics.jax.org/disease/155255" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://wormbase.org/resources/disease/DOID:0050902" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<span>
|
|
<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.">
|
|
|
|
</span>
|
|
</span>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
<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">
|
|
|
|
<div>
|
|
|
|
<a id="title" class="mim-anchor"></a>
|
|
|
|
<div>
|
|
<a id="number" class="mim-anchor"></a>
|
|
<div class="text-right">
|
|
|
|
|
|
|
|
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
|
|
|
|
<strong>SNOMEDCT:</strong> 1156923005, 443333004<br />
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 251858, 251863, 251867, 616<br />
|
|
|
|
|
|
<strong>DO:</strong> 0050902<br />
|
|
|
|
|
|
">ICD+</a>
|
|
|
|
</div>
|
|
<div>
|
|
<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
|
|
<span class="text-danger"><strong>#</strong></span>
|
|
155255
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
MEDULLOBLASTOMA; MDB
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
MEDULLOBLASTOMA PREDISPOSITION SYNDROME
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover 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>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/548?start=-3&limit=10&highlight=548">
|
|
1p34.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Medulloblastoma, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/155255"> 155255 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
PTCH2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603673"> 603673 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/1393?start=-3&limit=10&highlight=1393">
|
|
1q24.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Medulloblastoma predisposition syndrome}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/155255"> 155255 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>, <abbr class="mim-tip-hint" title="Somatic mutation">SMu</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
GPR161
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612250"> 612250 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/3/198?start=-3&limit=10&highlight=198">
|
|
3p22.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Medulloblastoma, somatic
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/155255"> 155255 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
CTNNB1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/116806"> 116806 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/9/397?start=-3&limit=10&highlight=397">
|
|
9q31.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Medulloblastoma}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/155255"> 155255 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>, <abbr class="mim-tip-hint" title="Somatic mutation">SMu</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
ELP1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603722"> 603722 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/10/521?start=-3&limit=10&highlight=521">
|
|
10q24.32
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Medulloblastoma}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/155255"> 155255 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>, <abbr class="mim-tip-hint" title="Somatic mutation">SMu</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
SUFU
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607035"> 607035 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/13/83?start=-3&limit=10&highlight=83">
|
|
13q13.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Medulloblastoma}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/155255"> 155255 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>, <abbr class="mim-tip-hint" title="Somatic mutation">SMu</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
BRCA2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600185"> 600185 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/155255" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/155255" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/155255" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Somatic mutation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/124975008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">124975008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866227&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866227</a>, <a href="https://bioportal.bioontology.org/search?q=C0544886&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0544886</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001442</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001442" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001442</a>]</span><br /> -
|
|
Autosomal dominant <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263681008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263681008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/771269000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">771269000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0443147&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0443147</a>, <a href="https://bioportal.bioontology.org/search?q=C1867440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1867440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000006</a>]</span><br /> -
|
|
Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEOPLASIA </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Medulloblastoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1156923005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1156923005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/443333004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">443333004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025149&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025149</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002885" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002885</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002885" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002885</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Isochromosome 17q frequent in cytogenetic studies <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4315918&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4315918</a>]</span><br /> -
|
|
Loss of heterozygosity for 17p sequences in 45% of medulloblastomas <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4315917&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4315917</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Incomplete penetrance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836598&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836598</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003829</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the SUFU negative regulator of hedgehog signaling gene (SUFU, <a href="/entry/607035#0005">607035.0005</a>)<br /> -
|
|
Caused by mutation in the BRCA2 gene (BRCA2, <a href="/entry/600185#0027">600185.0027</a>)<br /> -
|
|
Caused by somatic mutation in the catenin beta 1 gene (CTNNB1, <a href="/entry/116806#0007">116806.0007</a>)<br /> -
|
|
Caused by somatic mutation in the patched 2 gene (PTCH2, <a href="/entry/603673#0001">603673.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because medulloblastoma can be caused by germline mutations in several genes, including the SUFU gene (<a href="/entry/607035">607035</a>) on chromosome 10q24, the BRCA2 gene (<a href="/entry/600185">600185</a>) on chromosome 13q13, the ELP1 gene (<a href="/entry/603722">603722</a>) on chromosome 9q31, and the GPR161 gene (<a href="/entry/612250">612250</a>) on chromosome 1q24.</p><p>Somatic mutations in several genes have been found in sporadic cases of medulloblastoma. These genes include PTCH2 (<a href="/entry/603673">603673</a>) on chromosome 1p32 and CTNNB1 (<a href="/entry/116806">116806</a>) on chromosome 3p.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="description" class="mim-anchor"></a>
|
|
<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimDescriptionFold" class="collapse in ">
|
|
<span class="mim-text-font">
|
|
<p>Medulloblastoma is the most common brain tumor in children. It accounts for 16% of all pediatric brain tumors, and 40% of all cerebellar tumors in childhood are medulloblastoma. Medulloblastoma occurs bimodally, with peak incidences between 3 and 4 years and 8 and 9 years of age. Approximately 10 to 15% of medulloblastomas are diagnosed in infancy. Medulloblastoma accounts for less than 1% of central nervous system (CNS) tumors in adults, with highest incidence in adults 20 to 34 years of age. In 1 to 2% of patients, medulloblastoma is associated with Gorlin syndrome (<a href="/entry/109400">109400</a>), a nevoid basal carcinoma syndrome. Medulloblastoma also occurs in up to 40% of patients with Turcot syndrome (see <a href="/entry/276300">276300</a>). Medulloblastoma is thought to arise from neural stem cell precursors in the granular cell layer of the cerebellum. Standard treatment includes surgery, chemotherapy, and, depending on the age of the patient, radiation therapy (<a href="#7" class="mim-tip-reference" title="Crawford, J. R., MacDonald, T. J., Packer, R. J. <strong>Medulloblastoma in childhood: new biological advances.</strong> Lancet Neurol. 6: 1073-1085, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18031705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18031705</a>] [<a href="https://doi.org/10.1016/S1474-4422(07)70289-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18031705">Crawford et al., 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18031705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Millard, N. E., De Braganca, K. C. <strong>Medulloblastoma.</strong> J. Child Neurol. 31: 1341-1353, 2016. Note: Erratum: J. Child Neurol. 15Sept., 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26336203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26336203</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26336203[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/10.1177/0883073815600866" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26336203">Millard and De Braganca (2016)</a> reviewed the histopathologic variants and molecular subgroups of medulloblastoma. Pretreatment prognosis of medulloblastoma has been refined by histopathologic subclassification into the following variants: large-cell medulloblastoma, anaplastic medulloblastoma, desmoplastic/nodular medulloblastoma, and medulloblastoma with extensive nodularity (MBEN). The latter 2 groups have been shown to have a significantly superior prognosis as compared to the large cell and anaplastic groups in young children. At the molecular level, medulloblastomas have been categorized into the following subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4. Each subgroup is characterized by a unique set of genetics and gene expression as well as demographic and clinical features. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26336203" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#7" class="mim-tip-reference" title="Crawford, J. R., MacDonald, T. J., Packer, R. J. <strong>Medulloblastoma in childhood: new biological advances.</strong> Lancet Neurol. 6: 1073-1085, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18031705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18031705</a>] [<a href="https://doi.org/10.1016/S1474-4422(07)70289-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18031705">Crawford et al. (2007)</a> reviewed medulloblastoma, with a focus on clinical presentation, diagnosis, and treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18031705" 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>Cerebellar medulloblastoma is a feature of basal cell nevus syndrome (<a href="/entry/109400">109400</a>), von Hippel-Lindau syndrome (<a href="/entry/193300">193300</a>), and familial adenomatous polyposis (<a href="/entry/175100">175100</a>). In a formal risk analysis for brain tumors in familial adenomatous polyposis, <a href="#12" class="mim-tip-reference" title="Hamilton, S. R., Liu, B., Parsons, R. E., Papadopoulos, N., Jen, J., Powell, S. M., Krush, A. J., Berk, T., Cohen, Z., Tetu, B., Burger, P. C., Wood, P. A., Taqi, F., Booker, S. V., Petersen, G. M., Offerhaus, G. J. A., Tersmette, A. C., Giardiello, F. M., Vogelstein, B., Kinzler, K. W. <strong>The molecular basis of Turcot's syndrome.</strong> New Eng. J. Med. 332: 839-847, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7661930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7661930</a>] [<a href="https://doi.org/10.1056/NEJM199503303321302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7661930">Hamilton et al. (1995)</a> found that the relative risk of cerebellar medulloblastoma in patients with familial adenomatous polyposis was 92 times that for the general population (95% confidence interval, 29 to 269; p less than 0.001). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7661930" 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>Mutations in the SUFU Gene</em></strong></p><p>
|
|
Among 46 medulloblastomas, <a href="#31" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a> identified 4 from patients with a germline mutation in the SUFU gene. In 3 patients the germline mutation was truncating, and the wildtype allele was either deleted or mutated in the corresponding tumor. The fourth patient, who showed some features of nevoid basal cell carcinoma syndrome (NBCCS; <a href="/entry/109400">109400</a>) and was developmentally delayed, carried a germline contiguous gene deletion including the SUFU gene and a 'second hit' splice site mutation in intron 8 of SUFU. All 4 medulloblastomas were of the desmoplastic subtype. <a href="#31" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a> remarked that desmoplastic tumors make up 20 to 30% of medulloblastomas, have a more nodular architecture than classical medulloblastoma, and may have a better prognosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068298" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Brugieres, L., Pierron, G., Chompret, A., Bressac-de Paillerets, B., Di Rocco, F., Varlet, P., Pierre-Kahn, A., Caron, O., Grill, J., Delattre, O. <strong>Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations.</strong> J. Med. Genet. 47: 142-144, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19833601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19833601</a>] [<a href="https://doi.org/10.1136/jmg.2009.067751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19833601">Brugieres et al. (2010)</a> identified several children from 2 unrelated families with medulloblastoma and germline mutation in the SUFU gene. Among the 25 mutation carriers identified in the 2 families, 7 developed medulloblastomas, all before 3 years of age. All medulloblastomas in which the histology was reviewed were of the desmoplastic subtype, including 3 with the rare extensive nodularity subtype (MBEN). Three mutation carriers developed other tumors only in adulthood (breast cancer, leiomyosarcoma, and meningioma). Penetrance was estimated at 30%. <a href="#4" class="mim-tip-reference" title="Brugieres, L., Pierron, G., Chompret, A., Bressac-de Paillerets, B., Di Rocco, F., Varlet, P., Pierre-Kahn, A., Caron, O., Grill, J., Delattre, O. <strong>Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations.</strong> J. Med. Genet. 47: 142-144, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19833601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19833601</a>] [<a href="https://doi.org/10.1136/jmg.2009.067751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19833601">Brugieres et al. (2010)</a> noted the favorable outcome of the desmoplastic/nodular subtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19833601" 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>Mutations in the BRCA2 Gene</em></strong></p><p>
|
|
<a href="#27" class="mim-tip-reference" title="Reid, S., Renwick, A., Seal, S., Baskcomb, L., Barfoot, R., Jayatilake, H., The Breast Cancer Susceptibility Collaboration (UK), Pritchard-Jones, K., Stratton, M. R., Ridolfi-Luthy, A., Rahman, N. <strong>Biallelic BRCA2 mutations are associated with multiple malignancies in childhood including familial Wilms tumour. (Letter)</strong> J. Med. Genet. 42: 147-151, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15689453/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15689453</a>] [<a href="https://doi.org/10.1136/jmg.2004.022673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15689453">Reid et al. (2005)</a> studied 2 brothers with Wilms tumor (see <a href="/entry/194070">194070</a>) at 3.5 years and 7 months of age, respectively, and mutation in the BRCA2 gene. The younger brother developed medulloblastoma at 5 years of age that was treated with radiotherapy but relapsed at 12 years of age, resulting in his death. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15689453" 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>Mutations in the ELP1 Gene</em></strong></p><p>
|
|
<a href="#32" class="mim-tip-reference" title="Waszak, S. M., Robinson, G. W., Gudenas, B. L., Smith, K. S., Forget, A., Kojic, M., Garcia-Lopez, J., Hadley, J., Hamilton, K. V., Indersie, E., Buchhalter, I., Kerssemakers, J., and 51 others. <strong>Germline Elongator mutations in sonic hedgehog medulloblastoma.</strong> Nature 580: 396-401, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32296180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32296180</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32296180[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-020-2164-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32296180">Waszak et al. (2020)</a> identified germline ELP1 loss-of-function (LOF) variants in 29 (14%) of 202 pediatric patients with SHH (<a href="/entry/600725">600725</a>) pathway-activated medulloblastoma (MB-SHH). Germline ELP1 LOF variants were absent in 51 adult patients with MB-SHH. Whole-exome sequencing confirmed inheritance of pathogenic germline ELP1 LOF variants in 3 parent-offspring trios, and an assessment for family history of cancer was pursued for 2 patients. The first family revealed a notable familial history of cancer on the affected paternal side, with pediatric medulloblastoma in the father and the paternal aunt, as well as unspecified brain tumors in more distant paternal relatives. In the second family, a distant cousin on the affected maternal side had pediatric medulloblastoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32296180" 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>Mutations in the GPR161 Gene</em></strong></p><p>
|
|
<a href="#2" class="mim-tip-reference" title="Begemann, M., Waszak, S. M., Robinson, G. W., Jager, N., Sharma, T., Knopp, C., Kraft, F., Moser, O., Mynarek, M., Guerrini-Rousseau, L., Brugieres, L., Varlet, P., and 13 others. <strong>Germline GPR161 mutations predispose to pediatric medulloblastoma.</strong> J. Clin. Oncol. 38: 43-50, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31609649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31609649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31609649[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/10.1200/JCO.19.00577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31609649">Begemann et al. (2020)</a> reported 6 patients with infantile onset of medulloblastoma (median age 1.5 years) with the SHH signature and heterozygous germline mutations in the GPR161 gene. The index case, a female, developed a desmoplastic/nodular medulloblastoma, SHH-activated, TP53 (<a href="/entry/191170">191170</a>)-wildtype (WHO grade IV), at the age of 12 months. The tumor was resected, and she received chemotherapy and craniospinal radiation. At 16 years, she developed her first basal cell carcinoma (BCC) and by age 29 had developed an addition 10 BCCs, all within the radiation field and all amenable to surgical removal. At age 18 years, she underwent thyroidectomy for multinodular goiter. At 23 years of age she underwent excision of a rectal tubular adenoma with low-grade dysplasia, a low-grade intraepithelial neoplasia in the stomach, and several hyperplastic serrated polyps. At 24 years, a meningioma in the right temporal region was removed. She had microcephaly and mild frontal bossing and fulfilled some, but not all, criteria for Gorlin syndrome (<a href="/entry/109400">109400</a>). Her father, also a GPR161 mutation carrier, died at age 55 of adenocarcinoma of the colon. The proband's brother and 2 of his sons were carriers, with no reported neoplasia. The other 5 cases presented with medulloblastoma between 5 and 51 months. When last evaluated at ages 6 to 15 years, all had no evidence of disease or were in complete remission. None had new cancers. All had normal head circumference, and only the 2 who had received cranial radiation had developmental problems. One patient other than the index had family members with tumors. Three individuals were of European descent, 1 was from Ivory Coast, 1 from the Caribbean, and 1 of unknown ethnicity. Three of 6 had desmoplastic/nodular SHH type medulloblastoma, 2 had desmoplastic type, and 1 had classic type. All tumors showed LOH for GPR161, in 5 of 6 individuals due to 1q UPD, and in 1 due to a 425-kb focal deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31609649" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="pathogenesis" class="mim-anchor"></a>
|
|
<h4 href="#mimPathogenesisFold" id="mimPathogenesisToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimPathogenesisToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimPathogenesisFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Studying the molecular basis for metastasis in medulloblastoma, <a href="#17" class="mim-tip-reference" title="MacDonald, T. J., Brown, K. M., LaFleur, B., Peterson, K., Lawlor, C., Chen, Y., Packer, R. J., Cogen, P., Stephan, D. A. <strong>Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease.</strong> Nature Genet. 29: 143-152, 2001. Note: Erratum: Nature Genet. 35: 287 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11544480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11544480</a>] [<a href="https://doi.org/10.1038/ng731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11544480">MacDonald et al. (2001)</a> obtained expression profiles of 23 primary medulloblastomas clinically designated as either metastatic (M+) or nonmetastatic (M0) and identified 85 genes whose expression differed significantly between classes. They found that platelet-derived growth factor receptor-alpha (PDGFRA; <a href="/entry/173490">173490</a>) and members of the downstream Ras/mitogen-activated protein kinase (MAPK) signal transduction pathway are upregulated in M+ tumors. Immunohistochemical validation on an independent set of tumors showed significant overexpression of PDGFRA in M+ tumors compared to M0 tumors. Using in vitro assays, they showed that platelet-derived growth factor-alpha (PDGFA; <a href="/entry/173430">173430</a>) enhances medulloblastoma migration and increases phosphorylation of downstream MAP2K1 (<a href="/entry/176872">176872</a>), MAP2K2 (<a href="/entry/601263">601263</a>), MAPK1 (<a href="/entry/176948">176948</a>), and MAPK3 (<a href="/entry/601795">601795</a>) in a dose-dependent manner. <a href="#17" class="mim-tip-reference" title="MacDonald, T. J., Brown, K. M., LaFleur, B., Peterson, K., Lawlor, C., Chen, Y., Packer, R. J., Cogen, P., Stephan, D. A. <strong>Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease.</strong> Nature Genet. 29: 143-152, 2001. Note: Erratum: Nature Genet. 35: 287 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11544480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11544480</a>] [<a href="https://doi.org/10.1038/ng731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11544480">MacDonald et al. (2001)</a> suggested that inhibitors of PDGFRA and RAS proteins should be considered as possible novel therapeutic strategies against medulloblastoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11544480" 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="#9" class="mim-tip-reference" title="Gilbertson, R. J., Clifford, S. C. <strong>PDGFRB is overexpressed in metastatic medulloblastoma.</strong> Nature Genet. 35: 197-198, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14593398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14593398</a>] [<a href="https://doi.org/10.1038/ng1103-197" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14593398">Gilbertson and Clifford (2003)</a> stated that the oligonucleotide probe used by <a href="#17" class="mim-tip-reference" title="MacDonald, T. J., Brown, K. M., LaFleur, B., Peterson, K., Lawlor, C., Chen, Y., Packer, R. J., Cogen, P., Stephan, D. A. <strong>Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease.</strong> Nature Genet. 29: 143-152, 2001. Note: Erratum: Nature Genet. 35: 287 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11544480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11544480</a>] [<a href="https://doi.org/10.1038/ng731" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11544480">MacDonald et al. (2001)</a> to determine PDGFRA expression actually identified PDGFRB (<a href="/entry/173410">173410</a>), and therefore called into question whether PDGFRA or PDGFRB is regulated in invasive forms of medulloblastoma. <a href="#9" class="mim-tip-reference" title="Gilbertson, R. J., Clifford, S. C. <strong>PDGFRB is overexpressed in metastatic medulloblastoma.</strong> Nature Genet. 35: 197-198, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14593398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14593398</a>] [<a href="https://doi.org/10.1038/ng1103-197" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14593398">Gilbertson and Clifford (2003)</a> presented data confirming that PDGFRB is preferentially expressed in metastatic medulloblastoma and suggested that it may prove useful as a prognostic marker and as a therapeutic target for the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14593398+11544480" 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="#25" class="mim-tip-reference" title="Pomeroy, S. L., Tamayo, P., Gaasenbeek, M., Sturla, L. M., Angelo, M., McLaughlin, M. E., Kim, J. Y. H., Goumnerova, L. C., Black, P. M., Lau, C., Allen, J. C., Zagzag, D., and 13 others. <strong>Prediction of central nervous system embryonal tumour outcome based on gene expression.</strong> Nature 415: 436-442, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11807556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11807556</a>] [<a href="https://doi.org/10.1038/415436a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11807556">Pomeroy et al. (2002)</a> approached the problems of CNS tumor classification by developing a system based on DNA microarray gene expression data derived from 99 patient samples. They demonstrated that medulloblastomas are molecularly distinct from other brain tumors including primitive neuroectodermal tumors (PNETs), atypical teratoid/rhabdoid tumors (<a href="/entry/609322">609322</a>), and malignant gliomas. They also found evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic hedgehog pathway (see <a href="/entry/600725">600725</a>). <a href="#25" class="mim-tip-reference" title="Pomeroy, S. L., Tamayo, P., Gaasenbeek, M., Sturla, L. M., Angelo, M., McLaughlin, M. E., Kim, J. Y. H., Goumnerova, L. C., Black, P. M., Lau, C., Allen, J. C., Zagzag, D., and 13 others. <strong>Prediction of central nervous system embryonal tumour outcome based on gene expression.</strong> Nature 415: 436-442, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11807556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11807556</a>] [<a href="https://doi.org/10.1038/415436a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11807556">Pomeroy et al. (2002)</a> further showed that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumors at diagnosis. Malignant gliomas were clearly separable from medulloblastomas in that they express genes typical of the astrocytic and oligodendrocytic lineage. Medulloblastomas express ZIC (<a href="/entry/600470">600470</a>) and NSCL1 (<a href="/entry/162360">162360</a>), encoding transcription factors that are specific for cerebellar granule cells. <a href="#25" class="mim-tip-reference" title="Pomeroy, S. L., Tamayo, P., Gaasenbeek, M., Sturla, L. M., Angelo, M., McLaughlin, M. E., Kim, J. Y. H., Goumnerova, L. C., Black, P. M., Lau, C., Allen, J. C., Zagzag, D., and 13 others. <strong>Prediction of central nervous system embryonal tumour outcome based on gene expression.</strong> Nature 415: 436-442, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11807556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11807556</a>] [<a href="https://doi.org/10.1038/415436a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11807556">Pomeroy et al. (2002)</a> suggested that medulloblastomas, but not PNETs, arise from cerebellar granule cells, or alternatively, have activated the transcriptional program of cerebellar granule cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11807556" 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="Hallahan, A. R., Pritchard, J. I., Chandraratna, R. A. S., Ellenbogen, R. G., Geyer, J. R., Overland, R. P., Strand, A. D., Tapscott, S. J., Olson, J. M. <strong>BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect.</strong> Nature Med. 9: 1033-1038, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12872164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12872164</a>] [<a href="https://doi.org/10.1038/nm904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12872164">Hallahan et al. (2003)</a> established that retinoids cause extensive apoptosis of medulloblastoma cells. In a xenograft model, retinoids largely abrogated tumor growth. Using receptor-specific retinoid agonists, <a href="#11" class="mim-tip-reference" title="Hallahan, A. R., Pritchard, J. I., Chandraratna, R. A. S., Ellenbogen, R. G., Geyer, J. R., Overland, R. P., Strand, A. D., Tapscott, S. J., Olson, J. M. <strong>BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect.</strong> Nature Med. 9: 1033-1038, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12872164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12872164</a>] [<a href="https://doi.org/10.1038/nm904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12872164">Hallahan et al. (2003)</a> defined a subset of mRNAs that were induced by all active retinoids in retinoid-sensitive cell lines. They also identified BMP2 (<a href="/entry/112261">112261</a>) as a candidate mediator of retinoid activity. BMP2 protein induced medulloblastoma cell apoptosis, whereas the BMP2 antagonist Noggin (<a href="/entry/602991">602991</a>) blocked both retinoid and BMP2-induced apoptosis. BMP2 also induced p38 MAPK (<a href="/entry/600289">600289</a>), which is necessary for BMP2- and retinoid-induced apoptosis. Retinoid-resistant medulloblastoma cells underwent apoptosis when treated with BMP2 or when cultured with retinoid-sensitive medulloblastoma cells. Retinoid-induced expression of BMP2 is thus necessary and sufficient for apoptosis of retinoid-responsive cells, and expression of BMP2 by retinoid-sensitive cells is sufficient to induce apoptosis in surrounding retinoid-resistant cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12872164" 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="#16" class="mim-tip-reference" title="Leung, C., Lingbeek, M., Shakhova, O., Liu, J., Tanger, E., Saremasiani, P., van Lohuizen, M., Marino, S. <strong>Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas.</strong> Nature 428: 337-341, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15029199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15029199</a>] [<a href="https://doi.org/10.1038/nature02385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15029199">Leung et al. (2004)</a> demonstrated that BMI1 (<a href="/entry/164831">164831</a>) is strongly expressed in proliferating cerebellar precursor cells in mice and humans. Using Bmi1-null mice, <a href="#16" class="mim-tip-reference" title="Leung, C., Lingbeek, M., Shakhova, O., Liu, J., Tanger, E., Saremasiani, P., van Lohuizen, M., Marino, S. <strong>Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas.</strong> Nature 428: 337-341, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15029199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15029199</a>] [<a href="https://doi.org/10.1038/nature02385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15029199">Leung et al. (2004)</a> demonstrated a crucial role for BMI1 in clonal expansion of granule cell precursors both in vivo and in vitro. Deregulated proliferation of these progenitor cells, by activation of the Shh pathway, leads to medulloblastoma development. <a href="#16" class="mim-tip-reference" title="Leung, C., Lingbeek, M., Shakhova, O., Liu, J., Tanger, E., Saremasiani, P., van Lohuizen, M., Marino, S. <strong>Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas.</strong> Nature 428: 337-341, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15029199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15029199</a>] [<a href="https://doi.org/10.1038/nature02385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15029199">Leung et al. (2004)</a> also demonstrated linked overexpression of BMI1 and PTCH1 (<a href="/entry/601309">601309</a>), suggestive of SHH pathway activation, in a substantial fraction of primary human medulloblastomas. Together with the rapid induction of Bmi1 expression on addition of Shh or on overexpression of the Shh target Gli1 in cerebellar granule cell cultures, <a href="#16" class="mim-tip-reference" title="Leung, C., Lingbeek, M., Shakhova, O., Liu, J., Tanger, E., Saremasiani, P., van Lohuizen, M., Marino, S. <strong>Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas.</strong> Nature 428: 337-341, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15029199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15029199</a>] [<a href="https://doi.org/10.1038/nature02385" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15029199">Leung et al. (2004)</a> concluded that their findings implicate BMI1 overexpression as an alternative or additive mechanism in the pathogenesis of medulloblastomas, and highlight a role for BMI1-containing polycomb complexes in proliferation of cerebellar precursor cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15029199" 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>Because Drosophila Cic (<a href="/entry/612082">612082</a>) had been shown to mediate c-erbB (EGFR; see <a href="/entry/131550">131550</a>) signaling via transcriptional repression, <a href="#15" class="mim-tip-reference" title="Lee, C.-J., Chan, W.-I., Scotting, P. J. <strong>CIC, a gene involved in cerebellar development and ErbB signaling, is significantly expressed in medulloblastomas.</strong> J. Neurooncol. 73: 101-108, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981098</a>] [<a href="https://doi.org/10.1007/s11060-004-4598-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15981098">Lee et al. (2005)</a> studied the expression of human CIC in medulloblastoma, where high levels of ERBB2 (<a href="/entry/164870">164870</a>) and ERBB4 (<a href="/entry/600543">600543</a>) correlate with poor prognosis. In silico SAGE analysis of human normal and malignant brain demonstrated that medulloblastoma exhibited the highest level of CIC expression and that expression was most common in tumors of the central nervous system in general. RT-PCR and in situ hybridization verified the expression of CIC in tumor cells, although the level of expression varied between different medulloblastoma subtypes. In mouse postnatally developing cerebellum, in silico analysis and in situ hybridization indicated a strong correlation between Cic expression and the maturation profile of cerebellar granule cell precursors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15981098" 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="#22" class="mim-tip-reference" title="Northcott, P. A., Nakahara, Y., Wu, X., Feuk, L., Ellison, D. W., Croul, S., Mack, S., Kongkham, P. N., Peacock, J., Dubuc, A., Ra, Y.-S., Zilberberg, K., and 17 others. <strong>Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma.</strong> Nature Genet. 41: 465-472, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19270706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19270706</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19270706[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.336" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19270706">Northcott et al. (2009)</a> used high-resolution SNP genotyping to identify regions of genomic gain and loss in 212 medulloblastoma tumors. There were focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppressor genes, most not previously implicated in medulloblastoma. There were several amplifications and homozygous deletions, including highly focal genetic events, in genes targeting histone lysine methylation, particularly H3 histone (see <a href="/entry/602810">602810</a>) lysine-9 (H3K9). In vitro studies showed that restoring expression of genes controlling H3K9 methylation greatly diminished proliferation of medulloblastoma cells. <a href="#22" class="mim-tip-reference" title="Northcott, P. A., Nakahara, Y., Wu, X., Feuk, L., Ellison, D. W., Croul, S., Mack, S., Kongkham, P. N., Peacock, J., Dubuc, A., Ra, Y.-S., Zilberberg, K., and 17 others. <strong>Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma.</strong> Nature Genet. 41: 465-472, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19270706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19270706</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19270706[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.336" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19270706">Northcott et al. (2009)</a> postulated that defective control of the histone code may contribute to the pathogenesis of medulloblastoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19270706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Parsons, D. W., Li, M., Zhang, X., Jones, S., Leary, R. J., Lin, J. C.-H., Boca, S. M., Carter, H., Samayoa, J., Bettegowda, C., Gallia, G. L., Jallo, G. I., and 35 others. <strong>The genetic landscape of the childhood cancer medulloblastoma.</strong> Science 331: 435-439, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21163964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21163964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21163964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1198056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21163964">Parsons et al. (2011)</a> searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and microRNA genes using Sanger sequencing in a set of 22 medulloblastomas. <a href="#24" class="mim-tip-reference" title="Parsons, D. W., Li, M., Zhang, X., Jones, S., Leary, R. J., Lin, J. C.-H., Boca, S. M., Carter, H., Samayoa, J., Bettegowda, C., Gallia, G. L., Jallo, G. I., and 35 others. <strong>The genetic landscape of the childhood cancer medulloblastoma.</strong> Science 331: 435-439, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21163964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21163964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21163964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1198056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21163964">Parsons et al. (2011)</a> found that, on average, each tumor had 11 gene alterations, fewer by a factor of 5 to 10 than in the adult solid tumors that had been sequenced to that time. In addition to alterations in the Hedgehog (see <a href="/entry/600725">600725</a>) and Wnt pathways (see <a href="/entry/164820">164820</a>), their analysis led to the discovery of genes not known to be altered in medulloblastomas. Most notably, inactivating mutations of the histone-lysine N-methyltransferase genes MLL2 (<a href="/entry/602113">602113</a>) or MLL3 (<a href="/entry/606833">606833</a>) were identified in 16% of medulloblastoma patients. <a href="#24" class="mim-tip-reference" title="Parsons, D. W., Li, M., Zhang, X., Jones, S., Leary, R. J., Lin, J. C.-H., Boca, S. M., Carter, H., Samayoa, J., Bettegowda, C., Gallia, G. L., Jallo, G. I., and 35 others. <strong>The genetic landscape of the childhood cancer medulloblastoma.</strong> Science 331: 435-439, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21163964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21163964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21163964[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1198056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21163964">Parsons et al. (2011)</a> concluded that their results demonstrated key differences between the genetic landscapes of adult and childhood cancers, highlighted dysregulation of developmental pathways as an important mechanism underlying medulloblastomas, and identified a role for a specific type of histone methylation in human tumorigenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21163964" 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="Gibson, P., Tong, Y., Robinson, G., Thompson, M. C., Currle, D. S., Eden, C., Kranenburg, T. A., Hogg, T., Poppleton, H., Martin, J., Finkelstein, D., Pounds, S., and 21 others. <strong>Subtypes of medulloblastoma have distinct developmental origins.</strong> Nature 468: 1095-1099, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21150899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21150899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21150899[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/nature09587" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21150899">Gibson et al. (2010)</a> provided evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (<a href="/entry/116806">116806</a>) arises outside the cerebellum from cells of the dorsal brainstem. They found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip and embryonic dorsal brainstem than in the upper rhombic lip and developing cerebellum. MRI and intraoperative reports showed that human WNT-subtype tumors infiltrate the dorsal brainstem, whereas SHH-subtype tumors are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1+ precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 (<a href="/entry/191170">191170</a>) was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. The data of <a href="#8" class="mim-tip-reference" title="Gibson, P., Tong, Y., Robinson, G., Thompson, M. C., Currle, D. S., Eden, C., Kranenburg, T. A., Hogg, T., Poppleton, H., Martin, J., Finkelstein, D., Pounds, S., and 21 others. <strong>Subtypes of medulloblastoma have distinct developmental origins.</strong> Nature 468: 1095-1099, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21150899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21150899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21150899[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/nature09587" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21150899">Gibson et al. (2010)</a> provided the first evidence that subtypes of medulloblastoma have distinct cellular origins, and provided an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21150899" 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>Reviews</em></strong></p><p>
|
|
In their review, <a href="#7" class="mim-tip-reference" title="Crawford, J. R., MacDonald, T. J., Packer, R. J. <strong>Medulloblastoma in childhood: new biological advances.</strong> Lancet Neurol. 6: 1073-1085, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18031705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18031705</a>] [<a href="https://doi.org/10.1016/S1474-4422(07)70289-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18031705">Crawford et al. (2007)</a> provided an overview of the molecular biology of medulloblastoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18031705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Guessous, F., Li, Y., Abounader, R. <strong>Signaling pathways in medulloblastoma.</strong> J. Cell Physiol. 217: 577-583, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18651559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18651559</a>] [<a href="https://doi.org/10.1002/jcp.21542" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18651559">Guessous et al. (2008)</a> reviewed the involvement multiple signaling pathways in medulloblastoma malignancy, with a focus on their modes of deregulation, prognostic value, functional effects, cellular and molecular mechanisms of action, and implications for therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18651559" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="clinicalManagement" class="mim-anchor"></a>
|
|
<h4 href="#mimClinicalManagementFold" id="mimClinicalManagementToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimClinicalManagementToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimClinicalManagementFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#3" class="mim-tip-reference" title="Berman, D. M., Karhadkar, S. S., Hallahan, A. R., Pritchard, J. I., Eberhart, C. G., Watkins, D. N., Chen, J. K., Cooper, M. K., Taipale, J., Olson, J. M., Beachy, P. A. <strong>Medulloblastoma growth inhibition by hedgehog pathway blockade.</strong> Science 297: 1559-1561, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12202832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12202832</a>] [<a href="https://doi.org/10.1126/science.1073733" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12202832">Berman et al. (2002)</a> investigated therapeutic efficacy of the hedgehog pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. The compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, and thus established a specific role for hedgehog pathway activity in medulloblastoma growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12202832" 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="#29" class="mim-tip-reference" title="Rudin, C. M., Hann, C. L., Laterra, J., Yauch, R. L., Callahan, C. A., Fu, L., Holcomb, T., Stinson, J., Gould, S. E., Coleman, B., LoRusso, P. M., Von Hoff, D. D., de Sauvage, F. J., Low, J. A. <strong>Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449.</strong> New Eng. J. Med. 361: 1173-1178, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19726761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19726761</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19726761[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/10.1056/NEJMoa0902903" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19726761">Rudin et al. (2009)</a> described a 26-year-old man with metastatic medulloblastoma that was refractory to multiple therapies. Molecular analysis of the tumor specimens demonstrated activation of the hedgehog pathway, with loss of heterozygosity and somatic mutation of the gene encoding patched-1 (PTCH1; <a href="/entry/601309">601309</a>), a key negative regulator of hedgehog signaling. The patient was treated with a novel hedgehog pathway inhibitor, GDC-0449, and treatment resulted in a rapid, although transient, regression of the tumor and reduction of symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19726761" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="mapping" class="mim-anchor"></a>
|
|
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMappingFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Medulloblastoma Locus on Chromosome 17</em></strong></p><p>
|
|
A locus for medulloblastoma may map to chromosome 17p. Isochromosome 17q has been observed in high frequency in cytogenetic studies of medulloblastoma. By studies using restriction fragment length polymorphisms, <a href="#6" class="mim-tip-reference" title="Cogen, P. H., Daneshvar, L., Metzger, A. K., Edwards, M. S. B. <strong>Deletion mapping of the medulloblastoma locus on chromosome 17p.</strong> Genomics 8: 279-285, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1979050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1979050</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90283-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1979050">Cogen et al. (1990)</a> showed loss of heterozygosity for 17p sequences in 45% of medulloblastomas. The finding was predictive of a poor clinical response to treatment. Furthermore, a deletion could be mapped to 17p13.1-p12, the same chromosomal region for which loss of alleles has been shown in tumor specimens from patients with colon cancer, and the same region to which the p53 gene (<a href="/entry/191170">191170</a>) has been mapped. However, using denaturing gradient gel electrophoresis and direct sequencing, <a href="#5" class="mim-tip-reference" title="Cogen, P. H., Daneshvar, L., Metzger, A. K., Duyk, G., Edwards, M. S. B., Sheffield, V. C. <strong>Involvement of multiple chromosome 17p loci in medulloblastoma tumorigenesis.</strong> Am. J. Hum. Genet. 50: 584-589, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347196</a>]" pmid="1347196">Cogen et al. (1992)</a> detected p53 mutations in only 2 of 20 medulloblastoma specimens. Moreover, additional RFLP studies of these 20 specimens showed loss of heterozygosity at a more distal and distinct site, 17p13.3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1347196+1979050" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="molecularGenetics" class="mim-anchor"></a>
|
|
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>BRCA2 Mutations in Medulloblastomas</em></strong></p><p>
|
|
In 2 brothers who developed Wilms tumor (<a href="/entry/194070">194070</a>) and brain tumors, <a href="#27" class="mim-tip-reference" title="Reid, S., Renwick, A., Seal, S., Baskcomb, L., Barfoot, R., Jayatilake, H., The Breast Cancer Susceptibility Collaboration (UK), Pritchard-Jones, K., Stratton, M. R., Ridolfi-Luthy, A., Rahman, N. <strong>Biallelic BRCA2 mutations are associated with multiple malignancies in childhood including familial Wilms tumour. (Letter)</strong> J. Med. Genet. 42: 147-151, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15689453/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15689453</a>] [<a href="https://doi.org/10.1136/jmg.2004.022673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15689453">Reid et al. (2005)</a> identified 2 germline truncating BRCA2 mutations (<a href="/entry/600185#0027">600185.0027</a> and <a href="/entry/600185#0031">600185.0031</a>). One boy had recurrent medulloblastoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15689453" 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>SUFU Mutations in Desmoplastic Medulloblastomas and Medulloblastomas with Extensive Nodularity (MBEN)</em></strong></p><p>
|
|
<a href="#1" class="mim-tip-reference" title="Bayani, J., Zielenska, M., Marrano, P., Ng, Y. K., Taylor, M. D., Jay, V., Rutka, J. T., Squire, J. A. <strong>Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping.</strong> J. Neurosurg. 93: 437-448, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10969942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10969942</a>] [<a href="https://doi.org/10.3171/jns.2000.93.3.0437" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10969942">Bayani et al. (2000)</a> showed that loss of heterozygosity (LOH) on 10q24 is frequent in medulloblastomas, suggesting that this region contains one or more tumor suppressor genes. <a href="#31" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a> reported children with medulloblastoma who carried germline and somatic mutations in the SUFU gene (<a href="/entry/607035">607035</a>) accompanied by LOH of the wildtype allele. Several of these mutations encoded truncated proteins that were unable to export the GLI transcription factor (<a href="/entry/165220">165220</a>) from nucleus to cytoplasm, resulting in activation of SHH signaling. Thus, SUFU is a tumor suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway (MB-SHH). <a href="#31" class="mim-tip-reference" title="Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D. <strong>Mutations in SUFU predispose to medulloblastoma.</strong> Nature Genet. 31: 306-310, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>] [<a href="https://doi.org/10.1038/ng916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12068298">Taylor et al. (2002)</a> noted that all 4 medulloblastomas with SUFU truncating mutations were of the desmoplastic subtype. Desmoplastic tumors make up about 20 to 30% of medulloblastomas, have a more nodular architecture than 'classical' medulloblastoma, and may have a better prognosis. Activation of the SHH pathway is particularly high in desmoplastic medulloblastomas, as shown by increased expression of the SHH target genes GLI, SMOH (<a href="/entry/601500">601500</a>), and PTCH. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12068298+10969942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Brugieres, L., Pierron, G., Chompret, A., Bressac-de Paillerets, B., Di Rocco, F., Varlet, P., Pierre-Kahn, A., Caron, O., Grill, J., Delattre, O. <strong>Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations.</strong> J. Med. Genet. 47: 142-144, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19833601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19833601</a>] [<a href="https://doi.org/10.1136/jmg.2009.067751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19833601">Brugieres et al. (2010)</a> identified germline truncating SUFU mutations in 2 unrelated families with several children under 3 years of age diagnosed with medulloblastoma (<a href="/entry/607035#0005">607035.0005</a> and <a href="/entry/607035#0006">607035.0006</a>, respectively). Among the 25 mutation carriers in the 2 families, 7 developed medulloblastomas; of the 5 tumors for which histology was reviewed, 3 were classified as medulloblastoma with extensive nodularity (MBEN) and 2 were typical desmoplastic/nodular medulloblastoma. No obvious physical stigmata of nevoid basal cell carcinoma syndrome was found among 21 mutation carriers from both families who were examined, including 11 patients who underwent brain MRI. SUFU sequence analysis of 1 tumor from each family confirmed that only the mutant allele was detected in the tumor DNA, thus demonstrating the loss of the wildtype allele and supporting a tumor-suppressor role for SUFU. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19833601" 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>ELP1 Mutations in Medulloblastomas</em></strong></p><p>
|
|
<a href="#32" class="mim-tip-reference" title="Waszak, S. M., Robinson, G. W., Gudenas, B. L., Smith, K. S., Forget, A., Kojic, M., Garcia-Lopez, J., Hadley, J., Hamilton, K. V., Indersie, E., Buchhalter, I., Kerssemakers, J., and 51 others. <strong>Germline Elongator mutations in sonic hedgehog medulloblastoma.</strong> Nature 580: 396-401, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32296180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32296180</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32296180[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-020-2164-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32296180">Waszak et al. (2020)</a> analyzed all protein-coding genes and identified and replicated rare germline loss-of-function variants across the gene encoding elongator complex protein-1 (ELP1; <a href="/entry/603722">603722</a>) in 14% of pediatric patients with the medulloblastoma sonic hedgehog subgroup (MB-SHH). Parent-offspring and pedigree analysis identified 2 families with heterozygous germline ELP1 mutations and a history of pediatric medulloblastoma (<a href="/entry/603722#0004">603722.0004</a> and <a href="/entry/603722#0005">603722.0005</a>). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among pediatric patients with MB-SHH. ELP1-associated medulloblastomas were restricted to the SHH-alpha subtype and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1 (<a href="/entry/601309">601309</a>). Tumors from patients with ELP1-associated MB-SHH were characterized by a destabilized elongator complex, loss of elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to elongator deficiency in model systems. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32296180" 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>GPR161 Mutations in Medulloblastoma</em></strong></p><p>
|
|
In a 29-year-old German woman (M20769) who had had medulloblastoma at 12 months of age and who had an extensive history of other neoplasia, <a href="#2" class="mim-tip-reference" title="Begemann, M., Waszak, S. M., Robinson, G. W., Jager, N., Sharma, T., Knopp, C., Kraft, F., Moser, O., Mynarek, M., Guerrini-Rousseau, L., Brugieres, L., Varlet, P., and 13 others. <strong>Germline GPR161 mutations predispose to pediatric medulloblastoma.</strong> J. Clin. Oncol. 38: 43-50, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31609649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31609649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31609649[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/10.1200/JCO.19.00577" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31609649">Begemann et al. (2020)</a> identified a heterozygous germline frameshift mutation (<a href="/entry/612250#0002">612250.0002</a>) in the GPR161 gene. Analysis of 1,044 patients with medulloblastoma enrolled in previous sequencing studies revealed 2 additional unrelated patients (MB11_06 and SJMB335) with the heterozygous mutation. Three other patients carried 2 frameshift and a missense mutation, respectively. Each mutation occurred only once in gnomAD. Pathogenic variants in GPR161 were present only in medulloblastomas of the SHH subgroup and accounted for approximately 5% of those, similar to PTCH1 (<a href="/entry/601309">601309</a>) and SUFU (<a href="/entry/607035">607035</a>). Tumors in all GPR161-mutated individuals were TP53 (<a href="/entry/191170">191170</a>)-wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31609649" 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 in Medulloblastomas</em></strong></p><p>
|
|
Among 46 medulloblastomas derived from patients with sporadic disease, <a href="#13" class="mim-tip-reference" title="Huang, H., Mahler-Araujo, B. M., Sankila, A., Chimelli, L., Yonekawa, Y., Kleihues, P., Ohgaki, H. <strong>APC mutations in sporadic medulloblastomas.</strong> Am. J. Path. 156: 433-437, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10666372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10666372</a>] [<a href="https://doi.org/10.1016/S0002-9440(10)64747-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10666372">Huang et al. (2000)</a> identified 2 with somatic mutations in the APC gene and 4 with somatic mutations in the beta-catenin gene. This study provided the first evidence that APC mutations are operative in a subset of sporadic medulloblastomas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10666372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To identify mutations that drive medulloblastoma, <a href="#28" class="mim-tip-reference" title="Robinson, G., Parker, M., Kranenburg, T. A., Lu, C., Chen, X., Ding, L., Phoenix, T. N., Hedlund, E., Wei, L., Zhu, X., Chalhoub, N., Baker, S. J., and 38 others. <strong>Novel mutations target distinct subgroups of medulloblastoma.</strong> Nature 488: 43-48, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22722829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22722829</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22722829[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/nature11213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22722829">Robinson et al. (2012)</a> sequenced the entire genomes of 37 tumors and matched normal blood. One-hundred and thirty-six genes harboring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not theretofore implicated in medulloblastoma; several targeted distinct components of the epigenetic machinery in different disease subgroups, such as regulators of histone-3 lys27 (H3K27) and H3K4 trimethylation in subgroups 3 and 4 (e.g., KDM6A, <a href="/entry/300128">300128</a> and ZMYM3, <a href="/entry/300061">300061</a>), and beta-catenin-1 (CTNNB1; <a href="/entry/116806">116806</a>)-associated chromatin remodelers in WNT-subgroup tumors (e.g., SMARCA4, <a href="/entry/603254">603254</a> and CREBBP, <a href="/entry/600140">600140</a>). Modeling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumors identified genes that maintain this cell lineage (DDX3X; <a href="/entry/300160">300160</a>), as well as mutated genes that initiate (CDH1; <a href="/entry/192090">192090</a>) or cooperate (PIK3CA; <a href="/entry/171834">171834</a>) in tumorigenesis. <a href="#28" class="mim-tip-reference" title="Robinson, G., Parker, M., Kranenburg, T. A., Lu, C., Chen, X., Ding, L., Phoenix, T. N., Hedlund, E., Wei, L., Zhu, X., Chalhoub, N., Baker, S. J., and 38 others. <strong>Novel mutations target distinct subgroups of medulloblastoma.</strong> Nature 488: 43-48, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22722829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22722829</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22722829[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/nature11213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22722829">Robinson et al. (2012)</a> concluded that their data provided important new insights into the pathogenesis of medulloblastoma subgroups and highlighted targets for therapeutic development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22722829" 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="#23" class="mim-tip-reference" title="Northcott, P. A., Shih, D. J. H., Peacock, J., Garzia, L., Morrissy, A. S., Zichner, T., Stutz, A. M., Korshunov, A., Reimand, J., Schumacher, S. E., Beroukhim, R., Ellison, D. W., and 123 others. <strong>Subgroup-specific structural variation across 1,000 medulloblastoma genomes.</strong> Nature 488: 49-56, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22832581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22832581</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22832581[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/nature11327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22832581">Northcott et al. (2012)</a> reported somatic copy number aberrations in 1,087 unique medulloblastomas. These copy number variations are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP (<a href="/entry/603779">603779</a>), a gene associated with Parkinson disease (<a href="/entry/168600">168600</a>), which is exquisitely restricted to Group 4-alpha. Recurrent translocations of PVT1 (<a href="/entry/165140">165140</a>), including PVT1-MYC (<a href="/entry/190080">190080</a>) and PVT1-NDRG1 (<a href="/entry/605262">605262</a>), that arise through chromothripsis are restricted to Group 3. Numerous targetable somatic copy number aberrations, including recurrent events targeting TGF-beta (<a href="/entry/190180">190180</a>) signaling in Group 3, and NF-kappa-B (see <a href="/entry/164011">164011</a>) signaling in Group 4, suggested future avenues for rational, targeted therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22832581" 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="#14" class="mim-tip-reference" title="Jones, D. T. W., Jager, N., Kool, M., Zichner, T., Hutter, B., Sultan, M., Cho, Y.-J., Pugh, T. J., Hovestadt, V., Stutz, A. M., Rausch, T., Warnatz, H.-J., and 78 others. <strong>Dissecting the genomic complexity underlying medulloblastoma.</strong> Nature 488: 100-105, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22832583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22832583</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22832583[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/nature11284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22832583">Jones et al. (2012)</a> described an integrative deep-sequencing analysis of 125 tumor-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 medulloblastomas, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1; PTCH1, <a href="/entry/601309">601309</a>; MLL2, <a href="/entry/602113">602113</a>; SMARCA4) and in genes not previously linked to this tumor (DDX3X; CTDNEP1, <a href="/entry/610684">610684</a>; KDM6A, TBR1; <a href="/entry/604616">604616</a>), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of, to their knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22832583" 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 whole-exome sequencing of 92 primary medulloblastoma/normal pairs, <a href="#26" class="mim-tip-reference" title="Pugh, T. J., Weeraratne, S. D., Archer, T. C., Pomeranz Krummel, D. A., Auclair, D., Bochicchio, J., Carneiro, M. O., Carter, S. L., Cibulskis, K., Erlich, R. L., Greulich, H., Lawrence, M. S., and 31 others. <strong>Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.</strong> Nature 488: 106-110, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22820256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22820256</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22820256[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/nature11329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22820256">Pugh et al. (2012)</a> observed that overall, medulloblastomas have low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. <a href="#26" class="mim-tip-reference" title="Pugh, T. J., Weeraratne, S. D., Archer, T. C., Pomeranz Krummel, D. A., Auclair, D., Bochicchio, J., Carneiro, M. O., Carter, S. L., Cibulskis, K., Erlich, R. L., Greulich, H., Lawrence, M. S., and 31 others. <strong>Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.</strong> Nature 488: 106-110, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22820256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22820256</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22820256[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/nature11329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22820256">Pugh et al. (2012)</a> identified 12 genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4, and TP53 (<a href="/entry/191170">191170</a>). Recurrent somatic mutations were newly identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2 (<a href="/entry/601935">601935</a>), BCOR (<a href="/entry/300485">300485</a>), and LDB1 (<a href="/entry/603451">603451</a>). <a href="#26" class="mim-tip-reference" title="Pugh, T. J., Weeraratne, S. D., Archer, T. C., Pomeranz Krummel, D. A., Auclair, D., Bochicchio, J., Carneiro, M. O., Carter, S. L., Cibulskis, K., Erlich, R. L., Greulich, H., Lawrence, M. S., and 31 others. <strong>Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.</strong> Nature 488: 106-110, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22820256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22820256</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22820256[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/nature11329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22820256">Pugh et al. (2012)</a> showed that mutant DDX3X potentiates transactivation of a transcription factor (TCF4; <a href="/entry/602272">602272</a>) promoter and enhanced cell viability in combination with mutant, but not wildtype, beta-catenin. <a href="#26" class="mim-tip-reference" title="Pugh, T. J., Weeraratne, S. D., Archer, T. C., Pomeranz Krummel, D. A., Auclair, D., Bochicchio, J., Carneiro, M. O., Carter, S. L., Cibulskis, K., Erlich, R. L., Greulich, H., Lawrence, M. S., and 31 others. <strong>Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.</strong> Nature 488: 106-110, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22820256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22820256</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22820256[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/nature11329" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22820256">Pugh et al. (2012)</a> concluded that their study revealed the alteration of WNT, hedgehog, histone methyltransferase, and N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominated the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22820256" 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="Northcott, P. A., Buchhalter, I., Morrissy, A. S., Hovestadt, V., Weischenfeldt, J., Ehrenberger, T., Grobner, S., Segura-Wang, M., Zichner, T., Rudneva, V. A., Warnatz, H.-J., Sidiropoulos, N., and 75 others. <strong>The whole-genome landscape of medulloblastoma subtypes.</strong> Nature 547: 311-317, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28726821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28726821</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28726821[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/nature22973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28726821">Northcott et al. (2017)</a> analyzed the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analyzed cases, and identified subgroup-specific driver alterations that included novel actionable targets. Patients with Group 3 medulloblastomas were characterized by MYC (<a href="/entry/190080">190080</a>) amplifications. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 (<a href="/entry/617645">617645</a>) and 'enhancer hijacking' events that activate PRDM6 in patients with highly recurrent, stereotypical tandem duplications in the SNCAIP gene (<a href="/entry/603779">603779</a>), restricted to Group 4. <a href="#21" class="mim-tip-reference" title="Northcott, P. A., Buchhalter, I., Morrissy, A. S., Hovestadt, V., Weischenfeldt, J., Ehrenberger, T., Grobner, S., Segura-Wang, M., Zichner, T., Rudneva, V. A., Warnatz, H.-J., Sidiropoulos, N., and 75 others. <strong>The whole-genome landscape of medulloblastoma subtypes.</strong> Nature 547: 311-317, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28726821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28726821</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28726821[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/nature22973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28726821">Northcott et al. (2017)</a> concluded that the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28726821" 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="#30" class="mim-tip-reference" title="Suzuki, H., Kumar, S. A., Shuai, S., Diaz-Navarro, A., Gutierrez-Fernandez, A., De Antonellis, P., Cavalli, F. M. G., Juraschka, K., Farooq, H., Shibahara, I., Vladoiu, M. C., Zhang, J., and 56 others. <strong>Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.</strong> Nature 574: 707-711, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31664194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31664194</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31664194[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-019-1650-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31664194">Suzuki et al. (2019)</a> reported highly recurrent hotspot mutations (r.3A-G) of U1 spliceosomal small nuclear RNAs (U1 snRNAs; <a href="/entry/180680">180680</a>) in about 50% (56 of 109) of medulloblastomas caused by somatic mutation in SHH (<a href="/entry/600725">600725</a>). These mutations were not present across other subgroups of medulloblastoma, and <a href="#30" class="mim-tip-reference" title="Suzuki, H., Kumar, S. A., Shuai, S., Diaz-Navarro, A., Gutierrez-Fernandez, A., De Antonellis, P., Cavalli, F. M. G., Juraschka, K., Farooq, H., Shibahara, I., Vladoiu, M. C., Zhang, J., and 56 others. <strong>Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.</strong> Nature 574: 707-711, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31664194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31664194</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31664194[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s41586-019-1650-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31664194">Suzuki et al. (2019)</a> identified a U1 snRNA r.3A-G mutation in only 1 of 2,442 cancers comprising 36 other tumor types. The mutations occurred in 97% of adults (subtype SHH-delta) and 25% of adolescents (subtype SHH-alpha) with SHH medulloblastoma, but were largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5-prime splice site binding region, and snRNA-mutant tumors had significantly disrupted RNA splicing and an excess of 5-prime cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivated the tumor suppressor gene PTCH1 (<a href="/entry/601309">601309</a>) and activated oncogenes GLI2 (<a href="/entry/165230">165230</a>) and CCND2 (<a href="/entry/123833">123833</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31664194" 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>Deletions in DMBT1 in Medulloblastoma</em></strong></p><p>
|
|
<a href="#20" class="mim-tip-reference" title="Mollenhauer, J., Wiemann, S., Scheurlen, W., Korn, B., Hayashi, Y., Wilgenbus, K. K., van Deimling, A., Poustka, A. <strong>DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours.</strong> Nature Genet. 17: 32-39, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9288095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9288095</a>] [<a href="https://doi.org/10.1038/ng0997-32" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9288095">Mollenhauer et al. (1997)</a> identified the DMBT1 gene (<a href="/entry/601969">601969</a>) as the site of homozygous intragenic deletions at chromosome 10q25.3-q26.1 in medulloblastoma and glioblastoma multiforme tumor tissue, as well as in brain tumor cell lines. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9288095" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="animalModel" class="mim-anchor"></a>
|
|
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimAnimalModelFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#18" class="mim-tip-reference" title="Marino, S., Vooijs, M., van der Gulden, H., Jonker, J., Berns, A. <strong>Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum.</strong> Genes Dev. 14: 994-1004, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10783170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10783170</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10783170[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="10783170">Marino et al. (2000)</a> generated a mouse model for medulloblastoma by Cre-LoxP-mediated inactivation of Rb (RB1; <a href="/entry/614041">614041</a>) and p53 tumor suppressor genes in the cerebellar external granular layer (EGL) cells. Recombination mediated by Gfap (<a href="/entry/137780">137780</a>) promoter-driven Cre was found both in astrocytes and in immature precursor cells of the EGL in the developing cerebellum. Gfap-Cre-mediated inactivation of Rb in a p53-null background produced mice that developed highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma. These tumors were identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the EGL cells during development. <a href="#18" class="mim-tip-reference" title="Marino, S., Vooijs, M., van der Gulden, H., Jonker, J., Berns, A. <strong>Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum.</strong> Genes Dev. 14: 994-1004, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10783170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10783170</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10783170[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="10783170">Marino et al. (2000)</a> concluded that loss of function of Rb is essential for medulloblastoma development in the mouse and stated that their results strongly support the hypothesis that medulloblastomas arise from multipotent precursor cells located in the EGL. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10783170" 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>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="references"class="mim-anchor"></a>
|
|
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
|
|
<ol>
|
|
|
|
<li>
|
|
<a id="1" class="mim-anchor"></a>
|
|
<a id="Bayani2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bayani, J., Zielenska, M., Marrano, P., Ng, Y. K., Taylor, M. D., Jay, V., Rutka, J. T., Squire, J. A.
|
|
<strong>Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping.</strong>
|
|
J. Neurosurg. 93: 437-448, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10969942/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10969942</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10969942" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.3171/jns.2000.93.3.0437" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="2" class="mim-anchor"></a>
|
|
<a id="Begemann2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Begemann, M., Waszak, S. M., Robinson, G. W., Jager, N., Sharma, T., Knopp, C., Kraft, F., Moser, O., Mynarek, M., Guerrini-Rousseau, L., Brugieres, L., Varlet, P., and 13 others.
|
|
<strong>Germline GPR161 mutations predispose to pediatric medulloblastoma.</strong>
|
|
J. Clin. Oncol. 38: 43-50, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31609649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31609649</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31609649[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=31609649" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1200/JCO.19.00577" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Berman2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Berman, D. M., Karhadkar, S. S., Hallahan, A. R., Pritchard, J. I., Eberhart, C. G., Watkins, D. N., Chen, J. K., Cooper, M. K., Taipale, J., Olson, J. M., Beachy, P. A.
|
|
<strong>Medulloblastoma growth inhibition by hedgehog pathway blockade.</strong>
|
|
Science 297: 1559-1561, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12202832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12202832</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12202832" 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.1073733" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Brugieres2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Brugieres, L., Pierron, G., Chompret, A., Bressac-de Paillerets, B., Di Rocco, F., Varlet, P., Pierre-Kahn, A., Caron, O., Grill, J., Delattre, O.
|
|
<strong>Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations.</strong>
|
|
J. Med. Genet. 47: 142-144, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19833601/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19833601</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19833601" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2009.067751" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Cogen1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cogen, P. H., Daneshvar, L., Metzger, A. K., Duyk, G., Edwards, M. S. B., Sheffield, V. C.
|
|
<strong>Involvement of multiple chromosome 17p loci in medulloblastoma tumorigenesis.</strong>
|
|
Am. J. Hum. Genet. 50: 584-589, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1347196/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1347196</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1347196" 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="6" class="mim-anchor"></a>
|
|
<a id="Cogen1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Cogen, P. H., Daneshvar, L., Metzger, A. K., Edwards, M. S. B.
|
|
<strong>Deletion mapping of the medulloblastoma locus on chromosome 17p.</strong>
|
|
Genomics 8: 279-285, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1979050/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1979050</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1979050" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(90)90283-z" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Crawford2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Crawford, J. R., MacDonald, T. J., Packer, R. J.
|
|
<strong>Medulloblastoma in childhood: new biological advances.</strong>
|
|
Lancet Neurol. 6: 1073-1085, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18031705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18031705</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18031705" 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/S1474-4422(07)70289-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Gibson2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gibson, P., Tong, Y., Robinson, G., Thompson, M. C., Currle, D. S., Eden, C., Kranenburg, T. A., Hogg, T., Poppleton, H., Martin, J., Finkelstein, D., Pounds, S., and 21 others.
|
|
<strong>Subtypes of medulloblastoma have distinct developmental origins.</strong>
|
|
Nature 468: 1095-1099, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21150899/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21150899</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21150899[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=21150899" 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/nature09587" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Gilbertson2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gilbertson, R. J., Clifford, S. C.
|
|
<strong>PDGFRB is overexpressed in metastatic medulloblastoma.</strong>
|
|
Nature Genet. 35: 197-198, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14593398/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14593398</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14593398" 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/ng1103-197" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Guessous2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guessous, F., Li, Y., Abounader, R.
|
|
<strong>Signaling pathways in medulloblastoma.</strong>
|
|
J. Cell Physiol. 217: 577-583, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18651559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18651559</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18651559" 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/jcp.21542" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Hallahan2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hallahan, A. R., Pritchard, J. I., Chandraratna, R. A. S., Ellenbogen, R. G., Geyer, J. R., Overland, R. P., Strand, A. D., Tapscott, S. J., Olson, J. M.
|
|
<strong>BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect.</strong>
|
|
Nature Med. 9: 1033-1038, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12872164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12872164</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12872164" 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/nm904" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Hamilton1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hamilton, S. R., Liu, B., Parsons, R. E., Papadopoulos, N., Jen, J., Powell, S. M., Krush, A. J., Berk, T., Cohen, Z., Tetu, B., Burger, P. C., Wood, P. A., Taqi, F., Booker, S. V., Petersen, G. M., Offerhaus, G. J. A., Tersmette, A. C., Giardiello, F. M., Vogelstein, B., Kinzler, K. W.
|
|
<strong>The molecular basis of Turcot's syndrome.</strong>
|
|
New Eng. J. Med. 332: 839-847, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7661930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7661930</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7661930" 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/NEJM199503303321302" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Huang2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huang, H., Mahler-Araujo, B. M., Sankila, A., Chimelli, L., Yonekawa, Y., Kleihues, P., Ohgaki, H.
|
|
<strong>APC mutations in sporadic medulloblastomas.</strong>
|
|
Am. J. Path. 156: 433-437, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10666372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10666372</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10666372" 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/S0002-9440(10)64747-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Jones2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Jones, D. T. W., Jager, N., Kool, M., Zichner, T., Hutter, B., Sultan, M., Cho, Y.-J., Pugh, T. J., Hovestadt, V., Stutz, A. M., Rausch, T., Warnatz, H.-J., and 78 others.
|
|
<strong>Dissecting the genomic complexity underlying medulloblastoma.</strong>
|
|
Nature 488: 100-105, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22832583/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22832583</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22832583[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=22832583" 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/nature11284" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Lee2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lee, C.-J., Chan, W.-I., Scotting, P. J.
|
|
<strong>CIC, a gene involved in cerebellar development and ErbB signaling, is significantly expressed in medulloblastomas.</strong>
|
|
J. Neurooncol. 73: 101-108, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15981098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15981098</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15981098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s11060-004-4598-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Leung2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Leung, C., Lingbeek, M., Shakhova, O., Liu, J., Tanger, E., Saremasiani, P., van Lohuizen, M., Marino, S.
|
|
<strong>Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas.</strong>
|
|
Nature 428: 337-341, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15029199/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15029199</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15029199" 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/nature02385" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="MacDonald2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
MacDonald, T. J., Brown, K. M., LaFleur, B., Peterson, K., Lawlor, C., Chen, Y., Packer, R. J., Cogen, P., Stephan, D. A.
|
|
<strong>Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease.</strong>
|
|
Nature Genet. 29: 143-152, 2001. Note: Erratum: Nature Genet. 35: 287 only, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11544480/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11544480</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11544480" 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/ng731" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Marino2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Marino, S., Vooijs, M., van der Gulden, H., Jonker, J., Berns, A.
|
|
<strong>Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum.</strong>
|
|
Genes Dev. 14: 994-1004, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10783170/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10783170</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10783170[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=10783170" 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="19" class="mim-anchor"></a>
|
|
<a id="Millard2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Millard, N. E., De Braganca, K. C.
|
|
<strong>Medulloblastoma.</strong>
|
|
J. Child Neurol. 31: 1341-1353, 2016. Note: Erratum: J. Child Neurol. 15Sept., 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26336203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26336203</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26336203[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=26336203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1177/0883073815600866" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Mollenhauer1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mollenhauer, J., Wiemann, S., Scheurlen, W., Korn, B., Hayashi, Y., Wilgenbus, K. K., van Deimling, A., Poustka, A.
|
|
<strong>DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours.</strong>
|
|
Nature Genet. 17: 32-39, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9288095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9288095</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9288095" 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/ng0997-32" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Northcott2017" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Northcott, P. A., Buchhalter, I., Morrissy, A. S., Hovestadt, V., Weischenfeldt, J., Ehrenberger, T., Grobner, S., Segura-Wang, M., Zichner, T., Rudneva, V. A., Warnatz, H.-J., Sidiropoulos, N., and 75 others.
|
|
<strong>The whole-genome landscape of medulloblastoma subtypes.</strong>
|
|
Nature 547: 311-317, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28726821/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28726821</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28726821[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=28726821" 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/nature22973" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Northcott2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Northcott, P. A., Nakahara, Y., Wu, X., Feuk, L., Ellison, D. W., Croul, S., Mack, S., Kongkham, P. N., Peacock, J., Dubuc, A., Ra, Y.-S., Zilberberg, K., and 17 others.
|
|
<strong>Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma.</strong>
|
|
Nature Genet. 41: 465-472, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19270706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19270706</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19270706[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=19270706" 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.336" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Northcott2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Northcott, P. A., Shih, D. J. H., Peacock, J., Garzia, L., Morrissy, A. S., Zichner, T., Stutz, A. M., Korshunov, A., Reimand, J., Schumacher, S. E., Beroukhim, R., Ellison, D. W., and 123 others.
|
|
<strong>Subgroup-specific structural variation across 1,000 medulloblastoma genomes.</strong>
|
|
Nature 488: 49-56, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22832581/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22832581</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22832581[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=22832581" 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/nature11327" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Parsons2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Parsons, D. W., Li, M., Zhang, X., Jones, S., Leary, R. J., Lin, J. C.-H., Boca, S. M., Carter, H., Samayoa, J., Bettegowda, C., Gallia, G. L., Jallo, G. I., and 35 others.
|
|
<strong>The genetic landscape of the childhood cancer medulloblastoma.</strong>
|
|
Science 331: 435-439, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21163964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21163964</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21163964[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=21163964" 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.1198056" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Pomeroy2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pomeroy, S. L., Tamayo, P., Gaasenbeek, M., Sturla, L. M., Angelo, M., McLaughlin, M. E., Kim, J. Y. H., Goumnerova, L. C., Black, P. M., Lau, C., Allen, J. C., Zagzag, D., and 13 others.
|
|
<strong>Prediction of central nervous system embryonal tumour outcome based on gene expression.</strong>
|
|
Nature 415: 436-442, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11807556/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11807556</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11807556" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/415436a" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Pugh2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pugh, T. J., Weeraratne, S. D., Archer, T. C., Pomeranz Krummel, D. A., Auclair, D., Bochicchio, J., Carneiro, M. O., Carter, S. L., Cibulskis, K., Erlich, R. L., Greulich, H., Lawrence, M. S., and 31 others.
|
|
<strong>Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.</strong>
|
|
Nature 488: 106-110, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22820256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22820256</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22820256[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=22820256" 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/nature11329" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Reid2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reid, S., Renwick, A., Seal, S., Baskcomb, L., Barfoot, R., Jayatilake, H., The Breast Cancer Susceptibility Collaboration (UK), Pritchard-Jones, K., Stratton, M. R., Ridolfi-Luthy, A., Rahman, N.
|
|
<strong>Biallelic BRCA2 mutations are associated with multiple malignancies in childhood including familial Wilms tumour. (Letter)</strong>
|
|
J. Med. Genet. 42: 147-151, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15689453/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15689453</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15689453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmg.2004.022673" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Robinson2012" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Robinson, G., Parker, M., Kranenburg, T. A., Lu, C., Chen, X., Ding, L., Phoenix, T. N., Hedlund, E., Wei, L., Zhu, X., Chalhoub, N., Baker, S. J., and 38 others.
|
|
<strong>Novel mutations target distinct subgroups of medulloblastoma.</strong>
|
|
Nature 488: 43-48, 2012.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22722829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22722829</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22722829[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=22722829" 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/nature11213" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Rudin2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rudin, C. M., Hann, C. L., Laterra, J., Yauch, R. L., Callahan, C. A., Fu, L., Holcomb, T., Stinson, J., Gould, S. E., Coleman, B., LoRusso, P. M., Von Hoff, D. D., de Sauvage, F. J., Low, J. A.
|
|
<strong>Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449.</strong>
|
|
New Eng. J. Med. 361: 1173-1178, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19726761/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19726761</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19726761[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=19726761" 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/NEJMoa0902903" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Suzuki2019" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Suzuki, H., Kumar, S. A., Shuai, S., Diaz-Navarro, A., Gutierrez-Fernandez, A., De Antonellis, P., Cavalli, F. M. G., Juraschka, K., Farooq, H., Shibahara, I., Vladoiu, M. C., Zhang, J., and 56 others.
|
|
<strong>Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.</strong>
|
|
Nature 574: 707-711, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31664194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31664194</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31664194[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=31664194" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/s41586-019-1650-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Taylor2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D.
|
|
<strong>Mutations in SUFU predispose to medulloblastoma.</strong>
|
|
Nature Genet. 31: 306-310, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12068298/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12068298</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12068298" 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/ng916" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Waszak2020" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Waszak, S. M., Robinson, G. W., Gudenas, B. L., Smith, K. S., Forget, A., Kojic, M., Garcia-Lopez, J., Hadley, J., Hamilton, K. V., Indersie, E., Buchhalter, I., Kerssemakers, J., and 51 others.
|
|
<strong>Germline Elongator mutations in sonic hedgehog medulloblastoma.</strong>
|
|
Nature 580: 396-401, 2020.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32296180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32296180</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32296180[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=32296180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/s41586-020-2164-5" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="contributors" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="mim-text-font">
|
|
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 10/12/2022
|
|
</span>
|
|
</div>
|
|
</div>
|
|
<div class="row collapse" id="mimCollapseContributors">
|
|
<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">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 01/28/2021<br>Ada Hamosh - updated : 01/07/2020<br>Ada Hamosh - updated : 01/17/2018<br>Cassandra L. Kniffin - updated : 9/24/2012<br>Ada Hamosh - updated : 9/20/2012<br>Ada Hamosh - updated : 3/30/2011<br>Marla J. F. O'Neill - updated : 8/25/2010<br>Ada Hamosh - updated : 11/10/2009<br>Cassandra L. Kniffin - updated : 6/8/2009<br>Matthew B. Gross - updated : 9/30/2008<br>Ada Hamosh - updated : 5/21/2008<br>Cassandra L. Kniffin - updated : 1/28/2008<br>Marla J. F. O'Neill - updated : 3/17/2005<br>Ada Hamosh - updated : 4/7/2004<br>Victor A. McKusick - updated : 10/31/2003<br>Ada Hamosh - updated : 8/5/2003<br>Ada Hamosh - updated : 9/10/2002<br>Victor A. McKusick - updated : 6/18/2002<br>Ada Hamosh - updated : 1/22/2002<br>Victor A. McKusick - updated : 9/10/2001<br>Victor A. McKusick - updated : 3/9/2001<br>Patti M. Sherman - updated : 7/14/2000<br>Victor A. McKusick - updated : 9/2/1997
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="creationDate" class="mim-anchor"></a>
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 7/6/1990
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<a id="editHistory" class="mim-anchor"></a>
|
|
|
|
<div class="row">
|
|
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
|
<span class="text-nowrap mim-text-font">
|
|
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 10/17/2022
|
|
</span>
|
|
</div>
|
|
</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">
|
|
<span class="mim-text-font">
|
|
alopez : 10/13/2022<br>alopez : 10/12/2022<br>carol : 02/16/2022<br>carol : 10/14/2021<br>carol : 10/14/2021<br>carol : 10/13/2021<br>alopez : 01/28/2021<br>alopez : 11/24/2020<br>alopez : 01/07/2020<br>alopez : 01/17/2018<br>carol : 08/09/2016<br>mgross : 02/05/2013<br>carol : 9/26/2012<br>ckniffin : 9/24/2012<br>alopez : 9/21/2012<br>terry : 9/20/2012<br>carol : 6/4/2012<br>carol : 6/17/2011<br>terry : 4/28/2011<br>alopez : 3/30/2011<br>terry : 3/30/2011<br>wwang : 8/30/2010<br>terry : 8/25/2010<br>alopez : 11/12/2009<br>terry : 11/10/2009<br>wwang : 6/17/2009<br>wwang : 6/17/2009<br>ckniffin : 6/8/2009<br>carol : 10/9/2008<br>mgross : 9/30/2008<br>carol : 8/5/2008<br>alopez : 5/27/2008<br>terry : 5/21/2008<br>terry : 5/21/2008<br>carol : 2/5/2008<br>ckniffin : 1/28/2008<br>carol : 1/15/2008<br>mgross : 4/21/2005<br>wwang : 3/17/2005<br>alopez : 4/13/2004<br>terry : 4/7/2004<br>tkritzer : 11/6/2003<br>terry : 10/31/2003<br>alopez : 10/29/2003<br>alopez : 8/6/2003<br>terry : 8/5/2003<br>tkritzer : 9/10/2002<br>alopez : 7/25/2002<br>alopez : 6/20/2002<br>terry : 6/18/2002<br>alopez : 1/23/2002<br>terry : 1/22/2002<br>alopez : 10/15/2001<br>carol : 9/20/2001<br>terry : 9/10/2001<br>carol : 9/10/2001<br>carol : 3/23/2001<br>terry : 3/9/2001<br>mcapotos : 7/24/2000<br>mcapotos : 7/21/2000<br>psherman : 7/14/2000<br>carol : 2/25/1999<br>jenny : 9/3/1997<br>terry : 9/2/1997<br>mark : 5/14/1995<br>mimadm : 11/6/1994<br>carol : 5/1/1992<br>supermim : 3/16/1992<br>carol : 10/10/1990<br>carol : 7/13/1990
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div class="container visible-print-block">
|
|
|
|
<div class="row">
|
|
|
|
|
|
|
|
<div class="col-md-8 col-md-offset-1">
|
|
|
|
<div>
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
<strong>#</strong> 155255
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
MEDULLOBLASTOMA; MDB
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div >
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
MEDULLOBLASTOMA PREDISPOSITION SYNDROME
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 1156923005, 443333004;
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 251858, 251863, 251867, 616;
|
|
|
|
|
|
<strong>DO:</strong> 0050902;
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene 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>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
1p34.1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Medulloblastoma, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
155255
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
PTCH2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
603673
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
1q24.2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Medulloblastoma predisposition syndrome}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
155255
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive; Somatic mutation
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
GPR161
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
612250
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
3p22.1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Medulloblastoma, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
155255
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
CTNNB1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
116806
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
9q31.3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Medulloblastoma}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
155255
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive; Somatic mutation
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
ELP1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
603722
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
10q24.32
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Medulloblastoma}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
155255
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive; Somatic mutation
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
SUFU
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
607035
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
13q13.1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Medulloblastoma}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
155255
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant; Autosomal recessive; Somatic mutation
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
BRCA2
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
600185
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because medulloblastoma can be caused by germline mutations in several genes, including the SUFU gene (607035) on chromosome 10q24, the BRCA2 gene (600185) on chromosome 13q13, the ELP1 gene (603722) on chromosome 9q31, and the GPR161 gene (612250) on chromosome 1q24.</p><p>Somatic mutations in several genes have been found in sporadic cases of medulloblastoma. These genes include PTCH2 (603673) on chromosome 1p32 and CTNNB1 (116806) on chromosome 3p.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Medulloblastoma is the most common brain tumor in children. It accounts for 16% of all pediatric brain tumors, and 40% of all cerebellar tumors in childhood are medulloblastoma. Medulloblastoma occurs bimodally, with peak incidences between 3 and 4 years and 8 and 9 years of age. Approximately 10 to 15% of medulloblastomas are diagnosed in infancy. Medulloblastoma accounts for less than 1% of central nervous system (CNS) tumors in adults, with highest incidence in adults 20 to 34 years of age. In 1 to 2% of patients, medulloblastoma is associated with Gorlin syndrome (109400), a nevoid basal carcinoma syndrome. Medulloblastoma also occurs in up to 40% of patients with Turcot syndrome (see 276300). Medulloblastoma is thought to arise from neural stem cell precursors in the granular cell layer of the cerebellum. Standard treatment includes surgery, chemotherapy, and, depending on the age of the patient, radiation therapy (Crawford et al., 2007). </p><p>Millard and De Braganca (2016) reviewed the histopathologic variants and molecular subgroups of medulloblastoma. Pretreatment prognosis of medulloblastoma has been refined by histopathologic subclassification into the following variants: large-cell medulloblastoma, anaplastic medulloblastoma, desmoplastic/nodular medulloblastoma, and medulloblastoma with extensive nodularity (MBEN). The latter 2 groups have been shown to have a significantly superior prognosis as compared to the large cell and anaplastic groups in young children. At the molecular level, medulloblastomas have been categorized into the following subgroups: wingless (WNT), sonic hedgehog (SHH), group 3, and group 4. Each subgroup is characterized by a unique set of genetics and gene expression as well as demographic and clinical features. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Crawford et al. (2007) reviewed medulloblastoma, with a focus on clinical presentation, diagnosis, and treatment. </p><p>Cerebellar medulloblastoma is a feature of basal cell nevus syndrome (109400), von Hippel-Lindau syndrome (193300), and familial adenomatous polyposis (175100). In a formal risk analysis for brain tumors in familial adenomatous polyposis, Hamilton et al. (1995) found that the relative risk of cerebellar medulloblastoma in patients with familial adenomatous polyposis was 92 times that for the general population (95% confidence interval, 29 to 269; p less than 0.001). </p><p><strong><em>Mutations in the SUFU Gene</em></strong></p><p>
|
|
Among 46 medulloblastomas, Taylor et al. (2002) identified 4 from patients with a germline mutation in the SUFU gene. In 3 patients the germline mutation was truncating, and the wildtype allele was either deleted or mutated in the corresponding tumor. The fourth patient, who showed some features of nevoid basal cell carcinoma syndrome (NBCCS; 109400) and was developmentally delayed, carried a germline contiguous gene deletion including the SUFU gene and a 'second hit' splice site mutation in intron 8 of SUFU. All 4 medulloblastomas were of the desmoplastic subtype. Taylor et al. (2002) remarked that desmoplastic tumors make up 20 to 30% of medulloblastomas, have a more nodular architecture than classical medulloblastoma, and may have a better prognosis. </p><p>Brugieres et al. (2010) identified several children from 2 unrelated families with medulloblastoma and germline mutation in the SUFU gene. Among the 25 mutation carriers identified in the 2 families, 7 developed medulloblastomas, all before 3 years of age. All medulloblastomas in which the histology was reviewed were of the desmoplastic subtype, including 3 with the rare extensive nodularity subtype (MBEN). Three mutation carriers developed other tumors only in adulthood (breast cancer, leiomyosarcoma, and meningioma). Penetrance was estimated at 30%. Brugieres et al. (2010) noted the favorable outcome of the desmoplastic/nodular subtype. </p><p><strong><em>Mutations in the BRCA2 Gene</em></strong></p><p>
|
|
Reid et al. (2005) studied 2 brothers with Wilms tumor (see 194070) at 3.5 years and 7 months of age, respectively, and mutation in the BRCA2 gene. The younger brother developed medulloblastoma at 5 years of age that was treated with radiotherapy but relapsed at 12 years of age, resulting in his death. </p><p><strong><em>Mutations in the ELP1 Gene</em></strong></p><p>
|
|
Waszak et al. (2020) identified germline ELP1 loss-of-function (LOF) variants in 29 (14%) of 202 pediatric patients with SHH (600725) pathway-activated medulloblastoma (MB-SHH). Germline ELP1 LOF variants were absent in 51 adult patients with MB-SHH. Whole-exome sequencing confirmed inheritance of pathogenic germline ELP1 LOF variants in 3 parent-offspring trios, and an assessment for family history of cancer was pursued for 2 patients. The first family revealed a notable familial history of cancer on the affected paternal side, with pediatric medulloblastoma in the father and the paternal aunt, as well as unspecified brain tumors in more distant paternal relatives. In the second family, a distant cousin on the affected maternal side had pediatric medulloblastoma. </p><p><strong><em>Mutations in the GPR161 Gene</em></strong></p><p>
|
|
Begemann et al. (2020) reported 6 patients with infantile onset of medulloblastoma (median age 1.5 years) with the SHH signature and heterozygous germline mutations in the GPR161 gene. The index case, a female, developed a desmoplastic/nodular medulloblastoma, SHH-activated, TP53 (191170)-wildtype (WHO grade IV), at the age of 12 months. The tumor was resected, and she received chemotherapy and craniospinal radiation. At 16 years, she developed her first basal cell carcinoma (BCC) and by age 29 had developed an addition 10 BCCs, all within the radiation field and all amenable to surgical removal. At age 18 years, she underwent thyroidectomy for multinodular goiter. At 23 years of age she underwent excision of a rectal tubular adenoma with low-grade dysplasia, a low-grade intraepithelial neoplasia in the stomach, and several hyperplastic serrated polyps. At 24 years, a meningioma in the right temporal region was removed. She had microcephaly and mild frontal bossing and fulfilled some, but not all, criteria for Gorlin syndrome (109400). Her father, also a GPR161 mutation carrier, died at age 55 of adenocarcinoma of the colon. The proband's brother and 2 of his sons were carriers, with no reported neoplasia. The other 5 cases presented with medulloblastoma between 5 and 51 months. When last evaluated at ages 6 to 15 years, all had no evidence of disease or were in complete remission. None had new cancers. All had normal head circumference, and only the 2 who had received cranial radiation had developmental problems. One patient other than the index had family members with tumors. Three individuals were of European descent, 1 was from Ivory Coast, 1 from the Caribbean, and 1 of unknown ethnicity. Three of 6 had desmoplastic/nodular SHH type medulloblastoma, 2 had desmoplastic type, and 1 had classic type. All tumors showed LOH for GPR161, in 5 of 6 individuals due to 1q UPD, and in 1 due to a 425-kb focal deletion. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Studying the molecular basis for metastasis in medulloblastoma, MacDonald et al. (2001) obtained expression profiles of 23 primary medulloblastomas clinically designated as either metastatic (M+) or nonmetastatic (M0) and identified 85 genes whose expression differed significantly between classes. They found that platelet-derived growth factor receptor-alpha (PDGFRA; 173490) and members of the downstream Ras/mitogen-activated protein kinase (MAPK) signal transduction pathway are upregulated in M+ tumors. Immunohistochemical validation on an independent set of tumors showed significant overexpression of PDGFRA in M+ tumors compared to M0 tumors. Using in vitro assays, they showed that platelet-derived growth factor-alpha (PDGFA; 173430) enhances medulloblastoma migration and increases phosphorylation of downstream MAP2K1 (176872), MAP2K2 (601263), MAPK1 (176948), and MAPK3 (601795) in a dose-dependent manner. MacDonald et al. (2001) suggested that inhibitors of PDGFRA and RAS proteins should be considered as possible novel therapeutic strategies against medulloblastoma. </p><p>Gilbertson and Clifford (2003) stated that the oligonucleotide probe used by MacDonald et al. (2001) to determine PDGFRA expression actually identified PDGFRB (173410), and therefore called into question whether PDGFRA or PDGFRB is regulated in invasive forms of medulloblastoma. Gilbertson and Clifford (2003) presented data confirming that PDGFRB is preferentially expressed in metastatic medulloblastoma and suggested that it may prove useful as a prognostic marker and as a therapeutic target for the disease. </p><p>Pomeroy et al. (2002) approached the problems of CNS tumor classification by developing a system based on DNA microarray gene expression data derived from 99 patient samples. They demonstrated that medulloblastomas are molecularly distinct from other brain tumors including primitive neuroectodermal tumors (PNETs), atypical teratoid/rhabdoid tumors (609322), and malignant gliomas. They also found evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic hedgehog pathway (see 600725). Pomeroy et al. (2002) further showed that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumors at diagnosis. Malignant gliomas were clearly separable from medulloblastomas in that they express genes typical of the astrocytic and oligodendrocytic lineage. Medulloblastomas express ZIC (600470) and NSCL1 (162360), encoding transcription factors that are specific for cerebellar granule cells. Pomeroy et al. (2002) suggested that medulloblastomas, but not PNETs, arise from cerebellar granule cells, or alternatively, have activated the transcriptional program of cerebellar granule cells. </p><p>Hallahan et al. (2003) established that retinoids cause extensive apoptosis of medulloblastoma cells. In a xenograft model, retinoids largely abrogated tumor growth. Using receptor-specific retinoid agonists, Hallahan et al. (2003) defined a subset of mRNAs that were induced by all active retinoids in retinoid-sensitive cell lines. They also identified BMP2 (112261) as a candidate mediator of retinoid activity. BMP2 protein induced medulloblastoma cell apoptosis, whereas the BMP2 antagonist Noggin (602991) blocked both retinoid and BMP2-induced apoptosis. BMP2 also induced p38 MAPK (600289), which is necessary for BMP2- and retinoid-induced apoptosis. Retinoid-resistant medulloblastoma cells underwent apoptosis when treated with BMP2 or when cultured with retinoid-sensitive medulloblastoma cells. Retinoid-induced expression of BMP2 is thus necessary and sufficient for apoptosis of retinoid-responsive cells, and expression of BMP2 by retinoid-sensitive cells is sufficient to induce apoptosis in surrounding retinoid-resistant cells. </p><p>Leung et al. (2004) demonstrated that BMI1 (164831) is strongly expressed in proliferating cerebellar precursor cells in mice and humans. Using Bmi1-null mice, Leung et al. (2004) demonstrated a crucial role for BMI1 in clonal expansion of granule cell precursors both in vivo and in vitro. Deregulated proliferation of these progenitor cells, by activation of the Shh pathway, leads to medulloblastoma development. Leung et al. (2004) also demonstrated linked overexpression of BMI1 and PTCH1 (601309), suggestive of SHH pathway activation, in a substantial fraction of primary human medulloblastomas. Together with the rapid induction of Bmi1 expression on addition of Shh or on overexpression of the Shh target Gli1 in cerebellar granule cell cultures, Leung et al. (2004) concluded that their findings implicate BMI1 overexpression as an alternative or additive mechanism in the pathogenesis of medulloblastomas, and highlight a role for BMI1-containing polycomb complexes in proliferation of cerebellar precursor cells. </p><p>Because Drosophila Cic (612082) had been shown to mediate c-erbB (EGFR; see 131550) signaling via transcriptional repression, Lee et al. (2005) studied the expression of human CIC in medulloblastoma, where high levels of ERBB2 (164870) and ERBB4 (600543) correlate with poor prognosis. In silico SAGE analysis of human normal and malignant brain demonstrated that medulloblastoma exhibited the highest level of CIC expression and that expression was most common in tumors of the central nervous system in general. RT-PCR and in situ hybridization verified the expression of CIC in tumor cells, although the level of expression varied between different medulloblastoma subtypes. In mouse postnatally developing cerebellum, in silico analysis and in situ hybridization indicated a strong correlation between Cic expression and the maturation profile of cerebellar granule cell precursors. </p><p>Northcott et al. (2009) used high-resolution SNP genotyping to identify regions of genomic gain and loss in 212 medulloblastoma tumors. There were focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppressor genes, most not previously implicated in medulloblastoma. There were several amplifications and homozygous deletions, including highly focal genetic events, in genes targeting histone lysine methylation, particularly H3 histone (see 602810) lysine-9 (H3K9). In vitro studies showed that restoring expression of genes controlling H3K9 methylation greatly diminished proliferation of medulloblastoma cells. Northcott et al. (2009) postulated that defective control of the histone code may contribute to the pathogenesis of medulloblastoma. </p><p>Parsons et al. (2011) searched for copy number alterations using high-density microarrays and sequenced all known protein-coding genes and microRNA genes using Sanger sequencing in a set of 22 medulloblastomas. Parsons et al. (2011) found that, on average, each tumor had 11 gene alterations, fewer by a factor of 5 to 10 than in the adult solid tumors that had been sequenced to that time. In addition to alterations in the Hedgehog (see 600725) and Wnt pathways (see 164820), their analysis led to the discovery of genes not known to be altered in medulloblastomas. Most notably, inactivating mutations of the histone-lysine N-methyltransferase genes MLL2 (602113) or MLL3 (606833) were identified in 16% of medulloblastoma patients. Parsons et al. (2011) concluded that their results demonstrated key differences between the genetic landscapes of adult and childhood cancers, highlighted dysregulation of developmental pathways as an important mechanism underlying medulloblastomas, and identified a role for a specific type of histone methylation in human tumorigenesis. </p><p>Gibson et al. (2010) provided evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (116806) arises outside the cerebellum from cells of the dorsal brainstem. They found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip and embryonic dorsal brainstem than in the upper rhombic lip and developing cerebellum. MRI and intraoperative reports showed that human WNT-subtype tumors infiltrate the dorsal brainstem, whereas SHH-subtype tumors are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem which included aberrantly proliferating Zic1+ precursor cells. These lesions persisted in all mutant adult mice; moreover, in 15% of cases in which Tp53 (191170) was concurrently deleted, they progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. The data of Gibson et al. (2010) provided the first evidence that subtypes of medulloblastoma have distinct cellular origins, and provided an explanation for the marked molecular and clinical differences between SHH- and WNT-subtype medulloblastomas. </p><p><strong><em>Reviews</em></strong></p><p>
|
|
In their review, Crawford et al. (2007) provided an overview of the molecular biology of medulloblastoma. </p><p>Guessous et al. (2008) reviewed the involvement multiple signaling pathways in medulloblastoma malignancy, with a focus on their modes of deregulation, prognostic value, functional effects, cellular and molecular mechanisms of action, and implications for therapy. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Berman et al. (2002) investigated therapeutic efficacy of the hedgehog pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. The compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, and thus established a specific role for hedgehog pathway activity in medulloblastoma growth. </p><p>Rudin et al. (2009) described a 26-year-old man with metastatic medulloblastoma that was refractory to multiple therapies. Molecular analysis of the tumor specimens demonstrated activation of the hedgehog pathway, with loss of heterozygosity and somatic mutation of the gene encoding patched-1 (PTCH1; 601309), a key negative regulator of hedgehog signaling. The patient was treated with a novel hedgehog pathway inhibitor, GDC-0449, and treatment resulted in a rapid, although transient, regression of the tumor and reduction of symptoms. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Medulloblastoma Locus on Chromosome 17</em></strong></p><p>
|
|
A locus for medulloblastoma may map to chromosome 17p. Isochromosome 17q has been observed in high frequency in cytogenetic studies of medulloblastoma. By studies using restriction fragment length polymorphisms, Cogen et al. (1990) showed loss of heterozygosity for 17p sequences in 45% of medulloblastomas. The finding was predictive of a poor clinical response to treatment. Furthermore, a deletion could be mapped to 17p13.1-p12, the same chromosomal region for which loss of alleles has been shown in tumor specimens from patients with colon cancer, and the same region to which the p53 gene (191170) has been mapped. However, using denaturing gradient gel electrophoresis and direct sequencing, Cogen et al. (1992) detected p53 mutations in only 2 of 20 medulloblastoma specimens. Moreover, additional RFLP studies of these 20 specimens showed loss of heterozygosity at a more distal and distinct site, 17p13.3. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>BRCA2 Mutations in Medulloblastomas</em></strong></p><p>
|
|
In 2 brothers who developed Wilms tumor (194070) and brain tumors, Reid et al. (2005) identified 2 germline truncating BRCA2 mutations (600185.0027 and 600185.0031). One boy had recurrent medulloblastoma. </p><p><strong><em>SUFU Mutations in Desmoplastic Medulloblastomas and Medulloblastomas with Extensive Nodularity (MBEN)</em></strong></p><p>
|
|
Bayani et al. (2000) showed that loss of heterozygosity (LOH) on 10q24 is frequent in medulloblastomas, suggesting that this region contains one or more tumor suppressor genes. Taylor et al. (2002) reported children with medulloblastoma who carried germline and somatic mutations in the SUFU gene (607035) accompanied by LOH of the wildtype allele. Several of these mutations encoded truncated proteins that were unable to export the GLI transcription factor (165220) from nucleus to cytoplasm, resulting in activation of SHH signaling. Thus, SUFU is a tumor suppressor gene that predisposes individuals to medulloblastoma by modulating the SHH signaling pathway (MB-SHH). Taylor et al. (2002) noted that all 4 medulloblastomas with SUFU truncating mutations were of the desmoplastic subtype. Desmoplastic tumors make up about 20 to 30% of medulloblastomas, have a more nodular architecture than 'classical' medulloblastoma, and may have a better prognosis. Activation of the SHH pathway is particularly high in desmoplastic medulloblastomas, as shown by increased expression of the SHH target genes GLI, SMOH (601500), and PTCH. </p><p>Brugieres et al. (2010) identified germline truncating SUFU mutations in 2 unrelated families with several children under 3 years of age diagnosed with medulloblastoma (607035.0005 and 607035.0006, respectively). Among the 25 mutation carriers in the 2 families, 7 developed medulloblastomas; of the 5 tumors for which histology was reviewed, 3 were classified as medulloblastoma with extensive nodularity (MBEN) and 2 were typical desmoplastic/nodular medulloblastoma. No obvious physical stigmata of nevoid basal cell carcinoma syndrome was found among 21 mutation carriers from both families who were examined, including 11 patients who underwent brain MRI. SUFU sequence analysis of 1 tumor from each family confirmed that only the mutant allele was detected in the tumor DNA, thus demonstrating the loss of the wildtype allele and supporting a tumor-suppressor role for SUFU. </p><p><strong><em>ELP1 Mutations in Medulloblastomas</em></strong></p><p>
|
|
Waszak et al. (2020) analyzed all protein-coding genes and identified and replicated rare germline loss-of-function variants across the gene encoding elongator complex protein-1 (ELP1; 603722) in 14% of pediatric patients with the medulloblastoma sonic hedgehog subgroup (MB-SHH). Parent-offspring and pedigree analysis identified 2 families with heterozygous germline ELP1 mutations and a history of pediatric medulloblastoma (603722.0004 and 603722.0005). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among pediatric patients with MB-SHH. ELP1-associated medulloblastomas were restricted to the SHH-alpha subtype and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1 (601309). Tumors from patients with ELP1-associated MB-SHH were characterized by a destabilized elongator complex, loss of elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to elongator deficiency in model systems. </p><p><strong><em>GPR161 Mutations in Medulloblastoma</em></strong></p><p>
|
|
In a 29-year-old German woman (M20769) who had had medulloblastoma at 12 months of age and who had an extensive history of other neoplasia, Begemann et al. (2020) identified a heterozygous germline frameshift mutation (612250.0002) in the GPR161 gene. Analysis of 1,044 patients with medulloblastoma enrolled in previous sequencing studies revealed 2 additional unrelated patients (MB11_06 and SJMB335) with the heterozygous mutation. Three other patients carried 2 frameshift and a missense mutation, respectively. Each mutation occurred only once in gnomAD. Pathogenic variants in GPR161 were present only in medulloblastomas of the SHH subgroup and accounted for approximately 5% of those, similar to PTCH1 (601309) and SUFU (607035). Tumors in all GPR161-mutated individuals were TP53 (191170)-wildtype. </p><p><strong><em>Somatic Mutations in Medulloblastomas</em></strong></p><p>
|
|
Among 46 medulloblastomas derived from patients with sporadic disease, Huang et al. (2000) identified 2 with somatic mutations in the APC gene and 4 with somatic mutations in the beta-catenin gene. This study provided the first evidence that APC mutations are operative in a subset of sporadic medulloblastomas. </p><p>To identify mutations that drive medulloblastoma, Robinson et al. (2012) sequenced the entire genomes of 37 tumors and matched normal blood. One-hundred and thirty-six genes harboring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not theretofore implicated in medulloblastoma; several targeted distinct components of the epigenetic machinery in different disease subgroups, such as regulators of histone-3 lys27 (H3K27) and H3K4 trimethylation in subgroups 3 and 4 (e.g., KDM6A, 300128 and ZMYM3, 300061), and beta-catenin-1 (CTNNB1; 116806)-associated chromatin remodelers in WNT-subgroup tumors (e.g., SMARCA4, 603254 and CREBBP, 600140). Modeling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumors identified genes that maintain this cell lineage (DDX3X; 300160), as well as mutated genes that initiate (CDH1; 192090) or cooperate (PIK3CA; 171834) in tumorigenesis. Robinson et al. (2012) concluded that their data provided important new insights into the pathogenesis of medulloblastoma subgroups and highlighted targets for therapeutic development. </p><p>Northcott et al. (2012) reported somatic copy number aberrations in 1,087 unique medulloblastomas. These copy number variations are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP (603779), a gene associated with Parkinson disease (168600), which is exquisitely restricted to Group 4-alpha. Recurrent translocations of PVT1 (165140), including PVT1-MYC (190080) and PVT1-NDRG1 (605262), that arise through chromothripsis are restricted to Group 3. Numerous targetable somatic copy number aberrations, including recurrent events targeting TGF-beta (190180) signaling in Group 3, and NF-kappa-B (see 164011) signaling in Group 4, suggested future avenues for rational, targeted therapy. </p><p>Jones et al. (2012) described an integrative deep-sequencing analysis of 125 tumor-normal pairs, conducted as part of the International Cancer Genome Consortium (ICGC) PedBrain Tumor Project. Tetraploidy was identified as a frequent early event in Group 3 and 4 medulloblastomas, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1; PTCH1, 601309; MLL2, 602113; SMARCA4) and in genes not previously linked to this tumor (DDX3X; CTDNEP1, 610684; KDM6A, TBR1; 604616), often in subgroup-specific patterns. RNA sequencing confirmed these alterations, and revealed the expression of, to their knowledge, the first medulloblastoma fusion genes identified. Chromatin modifiers were frequently altered across all subgroups. </p><p>Using whole-exome sequencing of 92 primary medulloblastoma/normal pairs, Pugh et al. (2012) observed that overall, medulloblastomas have low mutation rates consistent with other pediatric tumors, with a median of 0.35 non-silent mutations per megabase. Pugh et al. (2012) identified 12 genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4, and TP53 (191170). Recurrent somatic mutations were newly identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2 (601935), BCOR (300485), and LDB1 (603451). Pugh et al. (2012) showed that mutant DDX3X potentiates transactivation of a transcription factor (TCF4; 602272) promoter and enhanced cell viability in combination with mutant, but not wildtype, beta-catenin. Pugh et al. (2012) concluded that their study revealed the alteration of WNT, hedgehog, histone methyltransferase, and N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominated the RNA helicase DDX3X as a component of pathogenic beta-catenin signaling in medulloblastoma. </p><p>Northcott et al. (2017) analyzed the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analyzed cases, and identified subgroup-specific driver alterations that included novel actionable targets. Patients with Group 3 medulloblastomas were characterized by MYC (190080) amplifications. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 (617645) and 'enhancer hijacking' events that activate PRDM6 in patients with highly recurrent, stereotypical tandem duplications in the SNCAIP gene (603779), restricted to Group 4. Northcott et al. (2017) concluded that the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma. </p><p>Suzuki et al. (2019) reported highly recurrent hotspot mutations (r.3A-G) of U1 spliceosomal small nuclear RNAs (U1 snRNAs; 180680) in about 50% (56 of 109) of medulloblastomas caused by somatic mutation in SHH (600725). These mutations were not present across other subgroups of medulloblastoma, and Suzuki et al. (2019) identified a U1 snRNA r.3A-G mutation in only 1 of 2,442 cancers comprising 36 other tumor types. The mutations occurred in 97% of adults (subtype SHH-delta) and 25% of adolescents (subtype SHH-alpha) with SHH medulloblastoma, but were largely absent from SHH medulloblastoma in infants. The U1 snRNA mutations occur in the 5-prime splice site binding region, and snRNA-mutant tumors had significantly disrupted RNA splicing and an excess of 5-prime cryptic splicing events. Alternative splicing mediated by mutant U1 snRNA inactivated the tumor suppressor gene PTCH1 (601309) and activated oncogenes GLI2 (165230) and CCND2 (123833). </p><p><strong><em>Deletions in DMBT1 in Medulloblastoma</em></strong></p><p>
|
|
Mollenhauer et al. (1997) identified the DMBT1 gene (601969) as the site of homozygous intragenic deletions at chromosome 10q25.3-q26.1 in medulloblastoma and glioblastoma multiforme tumor tissue, as well as in brain tumor cell lines. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Marino et al. (2000) generated a mouse model for medulloblastoma by Cre-LoxP-mediated inactivation of Rb (RB1; 614041) and p53 tumor suppressor genes in the cerebellar external granular layer (EGL) cells. Recombination mediated by Gfap (137780) promoter-driven Cre was found both in astrocytes and in immature precursor cells of the EGL in the developing cerebellum. Gfap-Cre-mediated inactivation of Rb in a p53-null background produced mice that developed highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma. These tumors were identified as early as 7 weeks of age on the outer surface of the molecular layer, corresponding to the location of the EGL cells during development. Marino et al. (2000) concluded that loss of function of Rb is essential for medulloblastoma development in the mouse and stated that their results strongly support the hypothesis that medulloblastomas arise from multipotent precursor cells located in the EGL. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bayani, J., Zielenska, M., Marrano, P., Ng, Y. K., Taylor, M. D., Jay, V., Rutka, J. T., Squire, J. A.
|
|
<strong>Molecular cytogenetic analysis of medulloblastomas and supratentorial primitive neuroectodermal tumors by using conventional banding, comparative genomic hybridization, and spectral karyotyping.</strong>
|
|
J. Neurosurg. 93: 437-448, 2000.
|
|
|
|
|
|
[PubMed: 10969942]
|
|
|
|
|
|
[Full Text: https://doi.org/10.3171/jns.2000.93.3.0437]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Begemann, M., Waszak, S. M., Robinson, G. W., Jager, N., Sharma, T., Knopp, C., Kraft, F., Moser, O., Mynarek, M., Guerrini-Rousseau, L., Brugieres, L., Varlet, P., and 13 others.
|
|
<strong>Germline GPR161 mutations predispose to pediatric medulloblastoma.</strong>
|
|
J. Clin. Oncol. 38: 43-50, 2020.
|
|
|
|
|
|
[PubMed: 31609649]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1200/JCO.19.00577]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Berman, D. M., Karhadkar, S. S., Hallahan, A. R., Pritchard, J. I., Eberhart, C. G., Watkins, D. N., Chen, J. K., Cooper, M. K., Taipale, J., Olson, J. M., Beachy, P. A.
|
|
<strong>Medulloblastoma growth inhibition by hedgehog pathway blockade.</strong>
|
|
Science 297: 1559-1561, 2002.
|
|
|
|
|
|
[PubMed: 12202832]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1073733]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Brugieres, L., Pierron, G., Chompret, A., Bressac-de Paillerets, B., Di Rocco, F., Varlet, P., Pierre-Kahn, A., Caron, O., Grill, J., Delattre, O.
|
|
<strong>Incomplete penetrance of the predisposition to medulloblastoma associated with germ-line SUFU mutations.</strong>
|
|
J. Med. Genet. 47: 142-144, 2010.
|
|
|
|
|
|
[PubMed: 19833601]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2009.067751]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cogen, P. H., Daneshvar, L., Metzger, A. K., Duyk, G., Edwards, M. S. B., Sheffield, V. C.
|
|
<strong>Involvement of multiple chromosome 17p loci in medulloblastoma tumorigenesis.</strong>
|
|
Am. J. Hum. Genet. 50: 584-589, 1992.
|
|
|
|
|
|
[PubMed: 1347196]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Cogen, P. H., Daneshvar, L., Metzger, A. K., Edwards, M. S. B.
|
|
<strong>Deletion mapping of the medulloblastoma locus on chromosome 17p.</strong>
|
|
Genomics 8: 279-285, 1990.
|
|
|
|
|
|
[PubMed: 1979050]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90283-z]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Crawford, J. R., MacDonald, T. J., Packer, R. J.
|
|
<strong>Medulloblastoma in childhood: new biological advances.</strong>
|
|
Lancet Neurol. 6: 1073-1085, 2007.
|
|
|
|
|
|
[PubMed: 18031705]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S1474-4422(07)70289-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gibson, P., Tong, Y., Robinson, G., Thompson, M. C., Currle, D. S., Eden, C., Kranenburg, T. A., Hogg, T., Poppleton, H., Martin, J., Finkelstein, D., Pounds, S., and 21 others.
|
|
<strong>Subtypes of medulloblastoma have distinct developmental origins.</strong>
|
|
Nature 468: 1095-1099, 2010.
|
|
|
|
|
|
[PubMed: 21150899]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature09587]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gilbertson, R. J., Clifford, S. C.
|
|
<strong>PDGFRB is overexpressed in metastatic medulloblastoma.</strong>
|
|
Nature Genet. 35: 197-198, 2003.
|
|
|
|
|
|
[PubMed: 14593398]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1103-197]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guessous, F., Li, Y., Abounader, R.
|
|
<strong>Signaling pathways in medulloblastoma.</strong>
|
|
J. Cell Physiol. 217: 577-583, 2008.
|
|
|
|
|
|
[PubMed: 18651559]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/jcp.21542]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hallahan, A. R., Pritchard, J. I., Chandraratna, R. A. S., Ellenbogen, R. G., Geyer, J. R., Overland, R. P., Strand, A. D., Tapscott, S. J., Olson, J. M.
|
|
<strong>BMP-2 mediates retinoid-induced apoptosis in medulloblastoma cells through a paracrine effect.</strong>
|
|
Nature Med. 9: 1033-1038, 2003.
|
|
|
|
|
|
[PubMed: 12872164]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nm904]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hamilton, S. R., Liu, B., Parsons, R. E., Papadopoulos, N., Jen, J., Powell, S. M., Krush, A. J., Berk, T., Cohen, Z., Tetu, B., Burger, P. C., Wood, P. A., Taqi, F., Booker, S. V., Petersen, G. M., Offerhaus, G. J. A., Tersmette, A. C., Giardiello, F. M., Vogelstein, B., Kinzler, K. W.
|
|
<strong>The molecular basis of Turcot's syndrome.</strong>
|
|
New Eng. J. Med. 332: 839-847, 1995.
|
|
|
|
|
|
[PubMed: 7661930]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM199503303321302]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huang, H., Mahler-Araujo, B. M., Sankila, A., Chimelli, L., Yonekawa, Y., Kleihues, P., Ohgaki, H.
|
|
<strong>APC mutations in sporadic medulloblastomas.</strong>
|
|
Am. J. Path. 156: 433-437, 2000.
|
|
|
|
|
|
[PubMed: 10666372]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S0002-9440(10)64747-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Jones, D. T. W., Jager, N., Kool, M., Zichner, T., Hutter, B., Sultan, M., Cho, Y.-J., Pugh, T. J., Hovestadt, V., Stutz, A. M., Rausch, T., Warnatz, H.-J., and 78 others.
|
|
<strong>Dissecting the genomic complexity underlying medulloblastoma.</strong>
|
|
Nature 488: 100-105, 2012.
|
|
|
|
|
|
[PubMed: 22832583]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11284]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lee, C.-J., Chan, W.-I., Scotting, P. J.
|
|
<strong>CIC, a gene involved in cerebellar development and ErbB signaling, is significantly expressed in medulloblastomas.</strong>
|
|
J. Neurooncol. 73: 101-108, 2005.
|
|
|
|
|
|
[PubMed: 15981098]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s11060-004-4598-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Leung, C., Lingbeek, M., Shakhova, O., Liu, J., Tanger, E., Saremasiani, P., van Lohuizen, M., Marino, S.
|
|
<strong>Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas.</strong>
|
|
Nature 428: 337-341, 2004.
|
|
|
|
|
|
[PubMed: 15029199]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature02385]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
MacDonald, T. J., Brown, K. M., LaFleur, B., Peterson, K., Lawlor, C., Chen, Y., Packer, R. J., Cogen, P., Stephan, D. A.
|
|
<strong>Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease.</strong>
|
|
Nature Genet. 29: 143-152, 2001. Note: Erratum: Nature Genet. 35: 287 only, 2003.
|
|
|
|
|
|
[PubMed: 11544480]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng731]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Marino, S., Vooijs, M., van der Gulden, H., Jonker, J., Berns, A.
|
|
<strong>Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum.</strong>
|
|
Genes Dev. 14: 994-1004, 2000.
|
|
|
|
|
|
[PubMed: 10783170]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Millard, N. E., De Braganca, K. C.
|
|
<strong>Medulloblastoma.</strong>
|
|
J. Child Neurol. 31: 1341-1353, 2016. Note: Erratum: J. Child Neurol. 15Sept., 2016.
|
|
|
|
|
|
[PubMed: 26336203]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1177/0883073815600866]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mollenhauer, J., Wiemann, S., Scheurlen, W., Korn, B., Hayashi, Y., Wilgenbus, K. K., van Deimling, A., Poustka, A.
|
|
<strong>DMBT1, a new member of the SRCR superfamily, on chromosome 10q25.3-26.1 is deleted in malignant brain tumours.</strong>
|
|
Nature Genet. 17: 32-39, 1997.
|
|
|
|
|
|
[PubMed: 9288095]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng0997-32]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Northcott, P. A., Buchhalter, I., Morrissy, A. S., Hovestadt, V., Weischenfeldt, J., Ehrenberger, T., Grobner, S., Segura-Wang, M., Zichner, T., Rudneva, V. A., Warnatz, H.-J., Sidiropoulos, N., and 75 others.
|
|
<strong>The whole-genome landscape of medulloblastoma subtypes.</strong>
|
|
Nature 547: 311-317, 2017.
|
|
|
|
|
|
[PubMed: 28726821]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature22973]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Northcott, P. A., Nakahara, Y., Wu, X., Feuk, L., Ellison, D. W., Croul, S., Mack, S., Kongkham, P. N., Peacock, J., Dubuc, A., Ra, Y.-S., Zilberberg, K., and 17 others.
|
|
<strong>Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma.</strong>
|
|
Nature Genet. 41: 465-472, 2009.
|
|
|
|
|
|
[PubMed: 19270706]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng.336]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Northcott, P. A., Shih, D. J. H., Peacock, J., Garzia, L., Morrissy, A. S., Zichner, T., Stutz, A. M., Korshunov, A., Reimand, J., Schumacher, S. E., Beroukhim, R., Ellison, D. W., and 123 others.
|
|
<strong>Subgroup-specific structural variation across 1,000 medulloblastoma genomes.</strong>
|
|
Nature 488: 49-56, 2012.
|
|
|
|
|
|
[PubMed: 22832581]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11327]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Parsons, D. W., Li, M., Zhang, X., Jones, S., Leary, R. J., Lin, J. C.-H., Boca, S. M., Carter, H., Samayoa, J., Bettegowda, C., Gallia, G. L., Jallo, G. I., and 35 others.
|
|
<strong>The genetic landscape of the childhood cancer medulloblastoma.</strong>
|
|
Science 331: 435-439, 2011.
|
|
|
|
|
|
[PubMed: 21163964]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1198056]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pomeroy, S. L., Tamayo, P., Gaasenbeek, M., Sturla, L. M., Angelo, M., McLaughlin, M. E., Kim, J. Y. H., Goumnerova, L. C., Black, P. M., Lau, C., Allen, J. C., Zagzag, D., and 13 others.
|
|
<strong>Prediction of central nervous system embryonal tumour outcome based on gene expression.</strong>
|
|
Nature 415: 436-442, 2002.
|
|
|
|
|
|
[PubMed: 11807556]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/415436a]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pugh, T. J., Weeraratne, S. D., Archer, T. C., Pomeranz Krummel, D. A., Auclair, D., Bochicchio, J., Carneiro, M. O., Carter, S. L., Cibulskis, K., Erlich, R. L., Greulich, H., Lawrence, M. S., and 31 others.
|
|
<strong>Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.</strong>
|
|
Nature 488: 106-110, 2012.
|
|
|
|
|
|
[PubMed: 22820256]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11329]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reid, S., Renwick, A., Seal, S., Baskcomb, L., Barfoot, R., Jayatilake, H., The Breast Cancer Susceptibility Collaboration (UK), Pritchard-Jones, K., Stratton, M. R., Ridolfi-Luthy, A., Rahman, N.
|
|
<strong>Biallelic BRCA2 mutations are associated with multiple malignancies in childhood including familial Wilms tumour. (Letter)</strong>
|
|
J. Med. Genet. 42: 147-151, 2005.
|
|
|
|
|
|
[PubMed: 15689453]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2004.022673]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Robinson, G., Parker, M., Kranenburg, T. A., Lu, C., Chen, X., Ding, L., Phoenix, T. N., Hedlund, E., Wei, L., Zhu, X., Chalhoub, N., Baker, S. J., and 38 others.
|
|
<strong>Novel mutations target distinct subgroups of medulloblastoma.</strong>
|
|
Nature 488: 43-48, 2012.
|
|
|
|
|
|
[PubMed: 22722829]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature11213]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rudin, C. M., Hann, C. L., Laterra, J., Yauch, R. L., Callahan, C. A., Fu, L., Holcomb, T., Stinson, J., Gould, S. E., Coleman, B., LoRusso, P. M., Von Hoff, D. D., de Sauvage, F. J., Low, J. A.
|
|
<strong>Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449.</strong>
|
|
New Eng. J. Med. 361: 1173-1178, 2009.
|
|
|
|
|
|
[PubMed: 19726761]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa0902903]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Suzuki, H., Kumar, S. A., Shuai, S., Diaz-Navarro, A., Gutierrez-Fernandez, A., De Antonellis, P., Cavalli, F. M. G., Juraschka, K., Farooq, H., Shibahara, I., Vladoiu, M. C., Zhang, J., and 56 others.
|
|
<strong>Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.</strong>
|
|
Nature 574: 707-711, 2019.
|
|
|
|
|
|
[PubMed: 31664194]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-019-1650-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Taylor, M. D., Liu, L., Raffel, C., Hui, C., Mainprize, T. G., Zhang, X., Agatep, R., Chiappa, S., Gao, L., Lowrance, A., Hao, A., Goldstein, A. M., Stavrou, T., Scherer, S. W., Dura, W. T., Wainwright, B., Squire, J. A., Rutka, J. T., Hogg, D.
|
|
<strong>Mutations in SUFU predispose to medulloblastoma.</strong>
|
|
Nature Genet. 31: 306-310, 2002.
|
|
|
|
|
|
[PubMed: 12068298]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng916]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Waszak, S. M., Robinson, G. W., Gudenas, B. L., Smith, K. S., Forget, A., Kojic, M., Garcia-Lopez, J., Hadley, J., Hamilton, K. V., Indersie, E., Buchhalter, I., Kerssemakers, J., and 51 others.
|
|
<strong>Germline Elongator mutations in sonic hedgehog medulloblastoma.</strong>
|
|
Nature 580: 396-401, 2020.
|
|
|
|
|
|
[PubMed: 32296180]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/s41586-020-2164-5]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Ada Hamosh - updated : 10/12/2022<br>Ada Hamosh - updated : 01/28/2021<br>Ada Hamosh - updated : 01/07/2020<br>Ada Hamosh - updated : 01/17/2018<br>Cassandra L. Kniffin - updated : 9/24/2012<br>Ada Hamosh - updated : 9/20/2012<br>Ada Hamosh - updated : 3/30/2011<br>Marla J. F. O'Neill - updated : 8/25/2010<br>Ada Hamosh - updated : 11/10/2009<br>Cassandra L. Kniffin - updated : 6/8/2009<br>Matthew B. Gross - updated : 9/30/2008<br>Ada Hamosh - updated : 5/21/2008<br>Cassandra L. Kniffin - updated : 1/28/2008<br>Marla J. F. O'Neill - updated : 3/17/2005<br>Ada Hamosh - updated : 4/7/2004<br>Victor A. McKusick - updated : 10/31/2003<br>Ada Hamosh - updated : 8/5/2003<br>Ada Hamosh - updated : 9/10/2002<br>Victor A. McKusick - updated : 6/18/2002<br>Ada Hamosh - updated : 1/22/2002<br>Victor A. McKusick - updated : 9/10/2001<br>Victor A. McKusick - updated : 3/9/2001<br>Patti M. Sherman - updated : 7/14/2000<br>Victor A. McKusick - updated : 9/2/1997
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Creation Date:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
Victor A. McKusick : 7/6/1990
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Edit History:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
alopez : 10/17/2022<br>alopez : 10/13/2022<br>alopez : 10/12/2022<br>carol : 02/16/2022<br>carol : 10/14/2021<br>carol : 10/14/2021<br>carol : 10/13/2021<br>alopez : 01/28/2021<br>alopez : 11/24/2020<br>alopez : 01/07/2020<br>alopez : 01/17/2018<br>carol : 08/09/2016<br>mgross : 02/05/2013<br>carol : 9/26/2012<br>ckniffin : 9/24/2012<br>alopez : 9/21/2012<br>terry : 9/20/2012<br>carol : 6/4/2012<br>carol : 6/17/2011<br>terry : 4/28/2011<br>alopez : 3/30/2011<br>terry : 3/30/2011<br>wwang : 8/30/2010<br>terry : 8/25/2010<br>alopez : 11/12/2009<br>terry : 11/10/2009<br>wwang : 6/17/2009<br>wwang : 6/17/2009<br>ckniffin : 6/8/2009<br>carol : 10/9/2008<br>mgross : 9/30/2008<br>carol : 8/5/2008<br>alopez : 5/27/2008<br>terry : 5/21/2008<br>terry : 5/21/2008<br>carol : 2/5/2008<br>ckniffin : 1/28/2008<br>carol : 1/15/2008<br>mgross : 4/21/2005<br>wwang : 3/17/2005<br>alopez : 4/13/2004<br>terry : 4/7/2004<br>tkritzer : 11/6/2003<br>terry : 10/31/2003<br>alopez : 10/29/2003<br>alopez : 8/6/2003<br>terry : 8/5/2003<br>tkritzer : 9/10/2002<br>alopez : 7/25/2002<br>alopez : 6/20/2002<br>terry : 6/18/2002<br>alopez : 1/23/2002<br>terry : 1/22/2002<br>alopez : 10/15/2001<br>carol : 9/20/2001<br>terry : 9/10/2001<br>carol : 9/10/2001<br>carol : 3/23/2001<br>terry : 3/9/2001<br>mcapotos : 7/24/2000<br>mcapotos : 7/21/2000<br>psherman : 7/14/2000<br>carol : 2/25/1999<br>jenny : 9/3/1997<br>terry : 9/2/1997<br>mark : 5/14/1995<br>mimadm : 11/6/1994<br>carol : 5/1/1992<br>supermim : 3/16/1992<br>carol : 10/10/1990<br>carol : 7/13/1990
|
|
</span>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div id="mimFooter">
|
|
|
|
|
|
<div class="container ">
|
|
<div class="row">
|
|
<br />
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="hidden-print mim-footer">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div class="visible-print-block mim-footer" style="position: relative;">
|
|
<div class="container">
|
|
<div class="row">
|
|
<p />
|
|
</div>
|
|
<div class="row text-center small">
|
|
NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers,
|
|
and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal
|
|
medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
|
|
<br />
|
|
OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
|
|
<br />
|
|
Copyright<sup>®</sup> 1966-2025 Johns Hopkins University.
|
|
<br />
|
|
Printed: March 13, 2025
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="modal fade" id="mimDonationPopupModal" tabindex="-1" role="dialog" aria-labelledby="mimDonationPopupModalTitle">
|
|
<div class="modal-dialog" role="document">
|
|
<div class="modal-content">
|
|
<div class="modal-header">
|
|
<button type="button" id="mimDonationPopupCancel" class="close" data-dismiss="modal" aria-label="Close"><span aria-hidden="true">×</span></button>
|
|
<h4 class="modal-title" id="mimDonationPopupModalTitle">
|
|
OMIM Donation:
|
|
</h4>
|
|
</div>
|
|
<div class="modal-body">
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Dear OMIM User,
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
To ensure long-term funding for the OMIM project, we have diversified
|
|
our revenue stream. We are determined to keep this website freely
|
|
accessible. Unfortunately, it is not free to produce. Expert curators
|
|
review the literature and organize it to facilitate your work. Over 90%
|
|
of the OMIM's operating expenses go to salary support for MD and PhD
|
|
science writers and biocurators. Please join your colleagues by making a
|
|
donation now and again in the future. Donations are an important
|
|
component of our efforts to ensure long-term funding to provide you the
|
|
information that you need at your fingertips.
|
|
</p>
|
|
</div>
|
|
</div>
|
|
<div class="row">
|
|
<div class="col-lg-offset-1 col-md-offset-1 col-sm-offset-1 col-xs-offset-1 col-lg-10 col-md-10 col-sm-10 col-xs-10">
|
|
<p>
|
|
Thank you in advance for your generous support, <br />
|
|
Ada Hamosh, MD, MPH <br />
|
|
Scientific Director, OMIM <br />
|
|
</p>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
<div class="modal-footer">
|
|
<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
</body>
|
|
|
|
</html>
|
|
|
|
|