4296 lines
388 KiB
Text
4296 lines
388 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
|
|
|
|
- #151623 - LI-FRAUMENI SYNDROME; LFS
|
|
|
|
|
|
- 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=151623"><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">#151623</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/151623"><strong>Clinical Synopsis</strong></a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
|
|
<a href="/phenotypicSeries/PS151623"> <strong>Phenotypic Series</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="#inheritance">Inheritance</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="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#otherFeatures">Other Features</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#heterogeneity">Heterogeneity</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#animalModel">Animal Model</a>
|
|
</li>
|
|
|
|
|
|
|
|
<li role="presentation" style="margin-left: 1em">
|
|
<a href="#history">History</a>
|
|
</li>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<li role="presentation">
|
|
<a href="#seeAlso"><strong>See Also</strong></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=LI-FRAUMENI SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=196&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1311/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
<div><a href="https://www.diseaseinfosearch.org/x/8745" 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=151623[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="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=524" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
</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:0111503" 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/151623" 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://omia.org/OMIA001990/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</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="mimCellLines">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
|
|
|
<div style="display: table-cell;">Cell Lines</div>
|
|
</div>
|
|
</a>
|
|
</span>
|
|
</span>
|
|
</div>
|
|
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
|
<div class="panel-body small mim-panel-body">
|
|
|
|
|
|
|
|
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:151623" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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> 428850001<br />
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 524<br />
|
|
|
|
|
|
<strong>DO:</strong> 0111503<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>
|
|
151623
|
|
</span>
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
LI-FRAUMENI SYNDROME; LFS
|
|
|
|
</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">
|
|
SARCOMA FAMILY SYNDROME OF LI AND FRAUMENI<br />
|
|
SBLA SYNDROME
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
LI-FRAUMENI-LIKE SYNDROME, INCLUDED; LFL, INCLUDED
|
|
</span>
|
|
</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/17/175?start=-3&limit=10&highlight=175">
|
|
17p13.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Li-Fraumeni syndrome
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/151623"> 151623 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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">
|
|
TP53
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/191170"> 191170 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/151623" 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">
|
|
|
|
<a href="/phenotypicSeries/PS151623" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', '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/151623" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/151623" 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">
|
|
|
|
- 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 />
|
|
|
|
</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">
|
|
|
|
- Breast cancer <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/254838004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">254838004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/254837009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">254837009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C50-C50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C50-C50</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/C50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0678222&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0678222</a>, <a href="https://bioportal.bioontology.org/search?q=C0006142&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0006142</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003002</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003002</a>]</span><br /> -
|
|
Soft tissue sarcomas <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/424413001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">424413001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1187396000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1187396000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/424952003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">424952003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551687&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551687</a>, <a href="https://bioportal.bioontology.org/search?q=C1261473&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1261473</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030448" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030448</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0100242" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100242</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030448" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030448</a>]</span><br /> -
|
|
Osteosarcomas <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1163405004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1163405004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/189878003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">189878003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029463&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029463</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002669" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002669</a>]</span><br /> -
|
|
Brain tumors <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/126952004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">126952004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/239.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">239.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0006118&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0006118</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030692" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030692</a>]</span><br /> -
|
|
Acute leukemias <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91855006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91855006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/24072005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">24072005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C95.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C95.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/C95.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C95.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/208.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">208.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085669&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085669</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002488" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002488</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002488" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002488</a>]</span><br /> -
|
|
Adrenocortical carcinomas <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/255035007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">255035007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/2227007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">2227007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0206686&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0206686</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006744</a>]</span><br /> -
|
|
Lung adenocarcinoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/254626006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">254626006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0152013&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152013</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030078" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030078</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030078" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030078</a>]</span><br /> -
|
|
Colon cancer <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/269533000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">269533000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/363510005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">363510005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/363406005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">363406005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C18.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C18.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/C18" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C18</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/153.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">153.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/153" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">153</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0346629&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0346629</a>, <a href="https://bioportal.bioontology.org/search?q=C0007102&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007102</a>, <a href="https://bioportal.bioontology.org/search?q=C0699790&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0699790</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003003</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003003</a>]</span><br /> -
|
|
Pancreatic cancer <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/372142002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">372142002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/363418001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">363418001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C25" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C25</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/C25.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C25.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/157.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">157.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/157" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">157</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235974&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235974</a>, <a href="https://bioportal.bioontology.org/search?q=C0346647&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0346647</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002894" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002894</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002894" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002894</a>]</span><br /> -
|
|
Prostate cancer <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/399068003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">399068003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/254900004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">254900004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C61" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C61</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/185" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">185</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0600139&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0600139</a>, <a href="https://bioportal.bioontology.org/search?q=C0376358&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0376358</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012125" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012125</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012125" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012125</a>]</span><br /> -
|
|
Wilms tumor <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25081006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25081006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302849000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027708&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027708</a>, <a href="https://bioportal.bioontology.org/search?q=C1333015&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1333015</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002667" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002667</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002667" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002667</a>]</span><br /> -
|
|
Phyllodes tumor <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D48.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D48.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0010701&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010701</a>]</span><br /> -
|
|
Choriocarcinoma, gestational <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/417057000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">417057000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/417570003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">417570003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349557&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349557</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">
|
|
|
|
- Increased risk of developing multiple primary cancers<br /> -
|
|
Early age of onset<br /> -
|
|
Penetrance by age 50 is 93% in female mutation carriers and 68% in male mutation carriers<br /> -
|
|
Female mutation carriers have earlier age at onset compared to male mutation carriers<br /> -
|
|
Gestational choriocarcinoma is seen in female partners of LFS patients after parental-fetal transmission of germline TP53 mutation from male carriers<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 tumor protein p53 (TP53, <a href="/entry/191170#0001">191170.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Li-Fraumeni syndrome
|
|
- <a href="/phenotypicSeries/PS151623">PS151623</a>
|
|
- 2 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/17/175?start=-3&limit=10&highlight=175"> 17p13.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/151623"> Li-Fraumeni syndrome </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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">
|
|
<a href="/entry/151623"> 151623 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/191170"> TP53 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/191170"> 191170 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/22/140?start=-3&limit=10&highlight=140"> 22q12.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609265"> Tumor predisposition syndrome 4, breast/prostate/colorectal </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">
|
|
<a href="/entry/609265"> 609265 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604373"> CHEK2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604373"> 604373 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" 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 Li-Fraumeni syndrome (LFS) is caused by heterozygous mutation in the p53 gene (TP53; <a href="/entry/191170">191170</a>) on chromosome 17p13.</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>Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous inherited cancer syndrome. LFS is characterized by autosomal dominant inheritance and early onset of tumors, multiple tumors within an individual, and multiple affected family members. In contrast to other inherited cancer syndromes, which are predominantly characterized by site-specific cancers, LFS presents with a variety of tumor types. The most common types are soft tissue sarcomas and osteosarcomas, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma. Classic LFS is defined as a proband with a sarcoma before the age of 45 years and a first-degree relative with any cancer before the age of 45 years and 1 additional first- or second-degree relative in the same lineage with any cancer before the age of 45 years or a sarcoma at any age (<a href="#26" class="mim-tip-reference" title="Li, F. P., Fraumeni, J. R., Jr., Mulvihill, J. J., Blattner, W. A., Dreyfus, M. G., Tucker, M. A., Miller, R. W. <strong>A cancer family syndrome in twenty-four kindreds.</strong> Cancer Res. 48: 5358-5362, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3409256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3409256</a>]" pmid="3409256">Li et al., 1988</a>). Li-Fraumeni-like syndrome (LFL) is defined as a proband with any childhood cancer, or a sarcoma, brain tumor, or adrenocortical tumor before the age of 45 years, plus a first- or second-degree relative in the same lineage with a typical LFS tumor at any age, and an additional first- or second-degree relative in the same lineage with any cancer before the age of 60 years (<a href="#6" class="mim-tip-reference" title="Birch, J. M., Hartley, A. L., Tricker, K. J., Prosser, J., Condie, A., Kelsey, A. M., Harris, M., Jones, P. H. M., Binchy, A., Crowther, D., Craft, A. W., Eden, O. B., Evans, D. G. R., Thompson, E., Mann, J. R., Martin, J., Mitchell, E. L. D., Santibanez-Koref, M. F. <strong>Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.</strong> Cancer Res. 54: 1298-1304, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8118819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8118819</a>]" pmid="8118819">Birch et al., 1994</a>). A less restrictive definition of LFL is 2 different LFS-related tumors in first- or second-degree relatives at any age (<a href="#10" class="mim-tip-reference" title="Eeles, R. A. <strong>Germline mutations in the TP53 gene.</strong> Cancer Surv. 25: 101-124, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8718514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8718514</a>]" pmid="8718514">Eeles, 1995</a>). Approximately 70% of LFS cases and 40% of LFL cases contain germline mutations in the p53 gene on chromosome 17p13.1 (<a href="#1" class="mim-tip-reference" title="Bachinski, L. L., Olufemi, S.-E., Zhou, X., Wu, C.-C., Yip, L., Shete, S., Lozano, G., Amos, C. I., Strong, L. C., Krahe, R. <strong>Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23.</strong> Cancer Res. 65: 427-431, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15695383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15695383</a>]" pmid="15695383">Bachinski et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8118819+8718514+3409256+15695383" 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>In reviewing medical records and death certificates of 648 childhood rhabdomyosarcoma patients, <a href="#25" class="mim-tip-reference" title="Li, F. P., Fraumeni, J. F. <strong>Rhabdomyosarcoma in children: an epidemiologic study and identification of a familial cancer syndrome.</strong> J. Nat. Cancer Inst. 43: 1365-1373, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5396222/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5396222</a>]" pmid="5396222">Li and Fraumeni (1969)</a> identified 4 families in which sibs or cousins had a childhood sarcoma. These 4 families also had striking histories of breast cancer and other neoplasms, suggesting a new familial cancer syndrome of diverse tumors. Subsequent prospective studies confirmed the high risk in family members of the tumor types that comprise LFS (<a href="#24" class="mim-tip-reference" title="Li, F. P., Fraumeni, J. F., Jr. <strong>Prospective study of a family cancer syndrome.</strong> JAMA 247: 2692-2694, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7077763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7077763</a>]" pmid="7077763">Li and Fraumeni, 1982</a>). Studies in other geographic and ethnic groups by Birch et al. (<a href="#5" class="mim-tip-reference" title="Birch, J. M., Hartley, A. L., Marsden, H. B., Harris, M., Swindell, R. <strong>Excess risk of breast cancer in the mothers of children with soft tissue sarcomas.</strong> Brit. J. Cancer 49: 325-331, 1984.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6704308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6704308</a>] [<a href="https://doi.org/10.1038/bjc.1984.51" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6704308">1984</a>, <a href="#4" class="mim-tip-reference" title="Birch, J. M., Hartley, A. L., Blair, V., Kelsey, A. M., Harris, M., Teare, M. D., Jones, P. H. M. <strong>Identification of factors associated with high breast cancer risk in the mothers of children with soft tissue sarcoma.</strong> J. Clin. Oncol. 8: 583-590, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2313328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2313328</a>] [<a href="https://doi.org/10.1200/JCO.1990.8.4.583" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2313328">1990</a>) corroborated the syndrome. The spectrum of cancers in the syndrome was shown to include, in addition to breast cancer and soft tissue sarcomas, brain tumors, osteosarcoma, leukemia, and adrenocortical carcinoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5396222+6704308+7077763+2313328" 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="Fraumeni, J. F., Jr., Wertelecki, W., Blattner, W. A., Jensen, R. D., Leventhal, B. G. <strong>Varied manifestations of a familial lymphoproliferative disorder.</strong> Am. J. Med. 59: 145-151, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/806230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">806230</a>] [<a href="https://doi.org/10.1016/0002-9343(75)90333-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="806230">Fraumeni et al. (1975)</a> described a kindred in which in 1 sibship of 9 adults, 4 died of lymphocytic or histiocytic lymphomas and 1, a male, of Waldenstrom macroglobulinemia complicated by adenocarcinoma of the lung. In the next generation, 1 person died of Hodgkin disease; 4 of 9 healthy persons had impaired lymphocyte transformation with phytohemagglutinin, and 3 of these had polyclonal elevation of IgM. Subsequent to the studies, adenocarcinoma of the lung developed in 1 of those with an immune defect, a woman, and her 3-year-old grandson developed lymphocytic leukemia. This was the first suggestion of a genetic or immunologic basis of lung adenocarcinoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=806230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#35" class="mim-tip-reference" title="Pearson, A. D. J., Craft, A. W., Ratcliffe, J. M., Birch, J. M., Morris-Jones, P., Roberts, D. F. <strong>Two families with the Li-Fraumeni cancer family syndrome.</strong> J. Med. Genet. 19: 362-365, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6958872/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6958872</a>] [<a href="https://doi.org/10.1136/jmg.19.5.362" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6958872">Pearson et al. (1982)</a> reported 2 families resembling that reported by <a href="#25" class="mim-tip-reference" title="Li, F. P., Fraumeni, J. F. <strong>Rhabdomyosarcoma in children: an epidemiologic study and identification of a familial cancer syndrome.</strong> J. Nat. Cancer Inst. 43: 1365-1373, 1969.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5396222/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5396222</a>]" pmid="5396222">Li and Fraumeni (1969)</a>. In 1, the mother had breast cancer and 3 of her 4 children had adrenocortical carcinoma, medulloblastoma, and rhabdomyosarcoma; in the other, the mother had breast cancer and 2 of her 3 children had adrenocortical carcinoma and rhabdomyosarcoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5396222+6958872" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#32" class="mim-tip-reference" title="Mulvihill, J. J. <strong>Personal Communication.</strong> Bethesda, Md. 6/11/1982."None>Mulvihill (1982)</a> used the designation sarcoma family syndrome of Li and Fraumeni for the familial association of breast cancer, soft tissue sarcoma, and other tumors. <a href="#18" class="mim-tip-reference" title="Hartley, A. L., Birch, J. M., Marsden, H. B., Harris, M. <strong>Malignant melanoma in families of children with osteosarcoma, chondrosarcoma, and adrenal cortical carcinoma.</strong> J. Med. Genet. 24: 664-668, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3480957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3480957</a>] [<a href="https://doi.org/10.1136/jmg.24.11.664" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3480957">Hartley et al. (1987)</a> referred to this as the SBLA syndrome, a designation derived from the tumors that occur in this cancer family syndrome: sarcoma, breast and brain tumors, leukemia, laryngeal and lung cancer, and adrenal cortical carcinoma (<a href="#29" class="mim-tip-reference" title="Lynch, H. T., Mulcahy, G. M., Harris, R. E., Guirgis, H. A., Lynch, J. F. <strong>Genetic and pathologic findings in a kindred with hereditary sarcoma breast cancer, brain tumors, leukemia, lung, laryngeal, and adrenal cortical carcinoma.</strong> Cancer 41: 2055-2064, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/647640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">647640</a>] [<a href="https://doi.org/10.1002/1097-0142(197805)41:5<2055::aid-cncr2820410554>3.0.co;2-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="647640">Lynch et al., 1978</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=647640+3480957" 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>Possible component tumors of LFS are melanoma, gonadal germ cell tumors, and carcinomas of the lung, pancreas, and prostate (<a href="#40" class="mim-tip-reference" title="Strong, L. C., Stine, M., Norsted, T. L. <strong>Cancer in survivors of childhood soft tissue sarcoma and their relatives.</strong> J. Nat. Cancer Inst. 79: 1213-1220, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3480372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3480372</a>]" pmid="3480372">Strong et al., 1987</a>; <a href="#26" class="mim-tip-reference" title="Li, F. P., Fraumeni, J. R., Jr., Mulvihill, J. J., Blattner, W. A., Dreyfus, M. G., Tucker, M. A., Miller, R. W. <strong>A cancer family syndrome in twenty-four kindreds.</strong> Cancer Res. 48: 5358-5362, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3409256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3409256</a>]" pmid="3409256">Li et al., 1988</a>). The diverse tumor types in family members characteristically develop at unusually early ages, and multiple primary tumors are frequent. By segregation analysis, <a href="#40" class="mim-tip-reference" title="Strong, L. C., Stine, M., Norsted, T. L. <strong>Cancer in survivors of childhood soft tissue sarcoma and their relatives.</strong> J. Nat. Cancer Inst. 79: 1213-1220, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3480372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3480372</a>]" pmid="3480372">Strong et al. (1987)</a> demonstrated that the observed cancer distribution in families best fit a rare autosomal dominant gene model. The model also predicted that in families at risk the probability of developing any invasive cancer (excluding carcinomas of the skin) reaches almost 50% by age 30, when only 1% of the general population has developed cancer. More than 90% of the gene carriers would develop cancer by age 70 (review by <a href="#30" class="mim-tip-reference" title="Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Jr., Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., Friend, S. H. <strong>Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.</strong> Science 250: 1233-1238, 1990. Note: Erratum: Science 259: 878 only, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1978757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1978757</a>] [<a href="https://doi.org/10.1126/science.1978757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1978757">Malkin et al., 1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1978757+3480372+3409256" 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="Hisada, M., Garber, J. E., Fung, C. Y., Fraumeni, J. F., Jr., Li, F. P. <strong>Multiple primary cancers in families with Li-Fraumeni syndrome.</strong> J. Nat. Cancer Inst. 90: 606-611, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554443</a>] [<a href="https://doi.org/10.1093/jnci/90.8.606" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9554443">Hisada et al. (1998)</a> quantified the incidence of second and third primary cancers in individuals from 24 LFS families originally diagnosed with cancer between 1968 and 1986. Among 200 LFS family members diagnosed with cancer, 30 (15%) developed a second cancer. Eight individuals (4%) had a third cancer, while 4 (2%) eventually developed a fourth cancer. Overall, the relative risk of occurrence of a second cancer was 5.3, with a cumulated probability of second cancer occurrence of 57% at 30 years after diagnosis of a first cancer. Relative risks of second cancers occurring in families with this syndrome were 83.0, 9.7, and 1.5 for individuals with a first cancer at ages 0 to 19 years, 20 to 44 years, and 45 years or more, respectively. Thirty (71%) of 42 subsequent cancers in this group were component cancers of LFS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9554443" 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="#31" class="mim-tip-reference" title="Masciari, S., Dewanwala, A., Stoffel, E. M., Lauwers, G. Y., Zheng, H., Achatz, M. I., Riegert-Johnson, D., Foretova, L., Silva, E. M., Digianni, L., Verselis, S. J., Schneider, K., Li, F. P., Fraumeni, J., Garber, J. E., Syngal, S. <strong>Gastric cancer in individuals with Li-Fraumeni syndrome.</strong> Genet. Med. 13: 651-657, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21552135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21552135</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21552135[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/10.1097/GIM.0b013e31821628b6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21552135">Masciari et al. (2011)</a> reviewed 62 TP53 mutation-positive families for gastric cancer. There were 429 cancer-affected individuals. In the 62 families gastric cancer was the diagnosis in the lineages of 21 (4.9%) subjects from 14 families (22.6%). The mean and median ages at gastric cancer diagnosis were 43 and 36 years, respectively (range: 24-74 years), significantly younger compared with the median age at diagnosis in the general population based on Surveillance Epidemiology and End Results data (71 years). Five (8.1%) families reported 2 or more cases of gastric cancer, and 6 (9.7%) families had cases of both colorectal and gastric cancers. No association was seen between phenotype and type/location of the TP53 mutations. Pathology review of the available tumors revealed both intestinal and diffuse histologies. <a href="#31" class="mim-tip-reference" title="Masciari, S., Dewanwala, A., Stoffel, E. M., Lauwers, G. Y., Zheng, H., Achatz, M. I., Riegert-Johnson, D., Foretova, L., Silva, E. M., Digianni, L., Verselis, S. J., Schneider, K., Li, F. P., Fraumeni, J., Garber, J. E., Syngal, S. <strong>Gastric cancer in individuals with Li-Fraumeni syndrome.</strong> Genet. Med. 13: 651-657, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21552135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21552135</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21552135[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/10.1097/GIM.0b013e31821628b6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21552135">Masciari et al. (2011)</a> concluded that early-onset gastric cancer seems to be a component of Li-Fraumeni syndrome, suggesting the need for early and regular endoscopic screening in individuals with germline TP53 mutations, particularly among those with a family history of gastric cancer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21552135" 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="inheritance" class="mim-anchor"></a>
|
|
<h4 href="#mimInheritanceFold" id="mimInheritanceToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimInheritanceToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimInheritanceFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Li-Fraumeni syndrome shows autosomal dominant inheritance. The lifetime penetrance is high: by age 50, women have an overall higher risk (93%) of developing cancer compared to men (68%), as well as an earlier age at onset (29 years in women vs 40 years in men). <a href="#16" class="mim-tip-reference" title="Gonzalez, K. D., Buzin, C. H., Noltner, K. A., Gu, D., Li, W., Malkin, D., Sommer, S. S. <strong>High frequency of de novo mutations in Li-Fraumeni syndrome.</strong> J. Med. Genet. 46: 689-693, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19556618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19556618</a>] [<a href="https://doi.org/10.1136/jmg.2008.058958" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19556618">Gonzalez et al. (2009)</a> identified TP53 mutations in 75 of 341 patients with early-onset cancer sent for TP53 testing. Family history was available for all 341 patients. Five (7%) of 75 patients with TP53 mutations were confirmed to have de novo mutations, and 4 (80%) of the 5 patients with de novo mutations had multiple primary cancers. Ten of 75 patients with TP53 mutations likely had de novo germline mutations by family history. <a href="#16" class="mim-tip-reference" title="Gonzalez, K. D., Buzin, C. H., Noltner, K. A., Gu, D., Li, W., Malkin, D., Sommer, S. S. <strong>High frequency of de novo mutations in Li-Fraumeni syndrome.</strong> J. Med. Genet. 46: 689-693, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19556618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19556618</a>] [<a href="https://doi.org/10.1136/jmg.2008.058958" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19556618">Gonzalez et al. (2009)</a> estimated that the frequency of de novo TP53 mutations resulting in Li-Fraumeni syndrome may be as high as 20% (15 of 75). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19556618" 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="#44" class="mim-tip-reference" title="Villani, A., Shore, A., Wasserman, J. D., Stephens, D., Kim, R. H., Druker, H., Gallinger, B., Naumer, A., Kohlmann, W., Novokmet, A., Tabori, U., Tijerin, M., Greer, M.-L. C., Finlay, J. L., Schiffman, J. D., Malkin, D. <strong>Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study.</strong> Lancet Oncol. 17: 1295-1305, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27501770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27501770</a>] [<a href="https://doi.org/10.1016/S1470-2045(16)30249-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27501770">Villani et al. (2016)</a> introduced a clinical surveillance program (The Toronto Protocol) using physical examination and frequent biochemical and imaging studies (consisting of whole body MRI, brain MRI, breast MRI, mammography, abdominal and pelvic ultrasound, and colonoscopy) at 3 tertiary care centers in Canada and the USA on January 1, 2004, for carriers of TP53 pathogenic variants. After confirmation of TP53 mutation, participants either chose to undergo surveillance or chose not to undergo surveillance. Patients could cross over between groups at any time. The primary outcome measure was detection of symptomatic tumors by surveillance investigations. The secondary outcome measure was 5-year overall survival established from a tumor diagnosed symptomatically (in the nonsurveillance group) versus one diagnosed by surveillance. <a href="#44" class="mim-tip-reference" title="Villani, A., Shore, A., Wasserman, J. D., Stephens, D., Kim, R. H., Druker, H., Gallinger, B., Naumer, A., Kohlmann, W., Novokmet, A., Tabori, U., Tijerin, M., Greer, M.-L. C., Finlay, J. L., Schiffman, J. D., Malkin, D. <strong>Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study.</strong> Lancet Oncol. 17: 1295-1305, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27501770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27501770</a>] [<a href="https://doi.org/10.1016/S1470-2045(16)30249-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27501770">Villani et al. (2016)</a> completed survival analyses using an as-treated approach. Between January 1, 2004 and July 1, 2015, <a href="#44" class="mim-tip-reference" title="Villani, A., Shore, A., Wasserman, J. D., Stephens, D., Kim, R. H., Druker, H., Gallinger, B., Naumer, A., Kohlmann, W., Novokmet, A., Tabori, U., Tijerin, M., Greer, M.-L. C., Finlay, J. L., Schiffman, J. D., Malkin, D. <strong>Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study.</strong> Lancet Oncol. 17: 1295-1305, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27501770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27501770</a>] [<a href="https://doi.org/10.1016/S1470-2045(16)30249-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27501770">Villani et al. (2016)</a> identified 89 carriers of TP53 pathogenic mutations in 39 unrelated families, of whom 40 (45%) agreed to surveillance and 49 (55%) declined surveillance. Nineteen patients (21%) crossed over from nonsurveillance to the surveillance group, giving a total of 59 individuals (66%) undergoing surveillance for a median of 32 months (IQR 12-87). Forty asymptomatic tumors have been detected in 19 (32%) of 59 patients who underwent surveillance. Two additional cancers were diagnosed between surveillance assessments (false negatives) and 2 biopsied lesions were nonneoplastic entities on pathologic review (false positives). Among the 49 individuals who initially declined surveillance, 61 symptomatic tumors were diagnosed in 43 patients (88%). Twenty-one (49%) of the 43 individuals not on surveillance who developed cancer were alive compared with 16 (84%) of the 19 individuals undergoing surveillance who developed cancer (p = 0.012) after a median follow-up of 46 months for those not on surveillance and 38 months for those on surveillance. Five-year overall survival was 88.8% (95% CI 78.7-100) in the surveillance group and 59.6% (47.2-75.2) in the nonsurveillance group (p = 0.0132). Based on these findings, <a href="#44" class="mim-tip-reference" title="Villani, A., Shore, A., Wasserman, J. D., Stephens, D., Kim, R. H., Druker, H., Gallinger, B., Naumer, A., Kohlmann, W., Novokmet, A., Tabori, U., Tijerin, M., Greer, M.-L. C., Finlay, J. L., Schiffman, J. D., Malkin, D. <strong>Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study.</strong> Lancet Oncol. 17: 1295-1305, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27501770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27501770</a>] [<a href="https://doi.org/10.1016/S1470-2045(16)30249-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27501770">Villani et al. (2016)</a> concluded that long-term compliance with a comprehensive surveillance protocol for early tumor detection in individuals with pathogenic TP53 variants is feasible and that early tumor detection through surveillance is associated with improved long-term survival. The authors suggested incorporation of this approach into clinical management of these patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27501770" 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>LFS1 results from mutation in the TP53 gene, which maps to chromosome 17p13.1.</p><p>To data on a set of kindreds with Li-Fraumeni syndrome, <a href="#36" class="mim-tip-reference" title="Shete, S., Amos, C. I., Hwang, S.-J., Strong, L. C. <strong>Individual-specific liability groups in genetic linkage, with applications to kindreds with Li-Fraumeni syndrome.</strong> Am. J. Hum. Genet. 70: 813-817, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11822026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11822026</a>] [<a href="https://doi.org/10.1086/339370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11822026">Shete et al. (2002)</a> applied a method they developed to incorporate individual-specific liability classes into linkage analysis. The approach yielded higher lod scores and more accurate estimates of the recombination fraction in the families showing linkage. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11822026" 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>Because tumor suppressor genes had been found to be associated with familial neoplasms, <a href="#30" class="mim-tip-reference" title="Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Jr., Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., Friend, S. H. <strong>Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.</strong> Science 250: 1233-1238, 1990. Note: Erratum: Science 259: 878 only, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1978757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1978757</a>] [<a href="https://doi.org/10.1126/science.1978757" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1978757">Malkin et al. (1990)</a> suspected mutation in this type of gene in LFS. The RB1 gene (<a href="/entry/614041">614041</a>) was an unlikely candidate for a germline mutation in LFS because retinoblastoma (<a href="/entry/180200">180200</a>) had not been observed in these families. On the other hand, the TP53 gene was a more likely candidate because inactivating mutations therein had been associated with sporadic osteosarcomas, soft tissue sarcomas, brain tumors, leukemias, and carcinomas of the lung and breast. Furthermore, transgenic mice carrying a mutant p53 gene have an increased incidence of osteosarcomas, soft tissue sarcomas, adenocarcinomas of the lung, and adrenal and lymphoid tumors--all tumors that occur as part of LFS. Such was the basis for the successful search for p53 mutations in this disorder (see <a href="/entry/191170#0001">191170.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1978757" 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 determine the frequency and distribution of germline p53 mutations in LFS families, <a href="#15" class="mim-tip-reference" title="Frebourg, T., Barbier, N., Yan, Y., Garber, J. E., Dreyfus, M., Fraumeni, J., Jr., Li, F. P., Friend, S. H. <strong>Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome.</strong> Am. J. Hum. Genet. 56: 608-615, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7887414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7887414</a>]" pmid="7887414">Frebourg et al. (1995)</a> sequenced the 10 coding exons of TP53 in lymphocytes and fibroblast cell lines derived from 15 families with the syndrome. Germline mutations were observed in 8 such families; of these, 6 were missense mutations located between exons 5 and 8. One mutation was a nonsense mutation in exon 6 and one was a splicing mutation in intron 4; each of these mutations generated aberrantly short p53 RNAs. The study indicated that most germline p53 mutations in LFS are located between exons 5 and 8 and that approximately 50% of patients with LFS have no germline mutations in the coding region of the p53 gene. Significantly, in 3 families, a mutation of the p53 gene was observed in a fibroblast cell line derived from the proband, but the mutation was not found in affected relatives in 2 families or in the blood from 1 of the probands. This indicated that the mutation probably occurred during cell culture; thus, it is necessary that analysis for germline p53 mutations be performed on cells that have not been grown in vitro. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7887414" 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="#41" class="mim-tip-reference" title="Varley, J. M., Evans, D. G. R., Birch, J. M. <strong>Li-Fraumeni syndrome: a molecular and clinical review.</strong> Brit. J. Cancer 76: 1-14, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9218725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9218725</a>] [<a href="https://doi.org/10.1038/bjc.1997.328" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9218725">Varley et al. (1997)</a> stated that more than 50 families had been identified with LFS caused by germline TP53 mutations. LFS is defined by strict clinical criteria, described by <a href="#26" class="mim-tip-reference" title="Li, F. P., Fraumeni, J. R., Jr., Mulvihill, J. J., Blattner, W. A., Dreyfus, M. G., Tucker, M. A., Miller, R. W. <strong>A cancer family syndrome in twenty-four kindreds.</strong> Cancer Res. 48: 5358-5362, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3409256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3409256</a>]" pmid="3409256">Li et al. (1988)</a>. This definition has been relaxed to include Li-Fraumeni-like (LFL) cases (<a href="#6" class="mim-tip-reference" title="Birch, J. M., Hartley, A. L., Tricker, K. J., Prosser, J., Condie, A., Kelsey, A. M., Harris, M., Jones, P. H. M., Binchy, A., Crowther, D., Craft, A. W., Eden, O. B., Evans, D. G. R., Thompson, E., Mann, J. R., Martin, J., Mitchell, E. L. D., Santibanez-Koref, M. F. <strong>Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.</strong> Cancer Res. 54: 1298-1304, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8118819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8118819</a>]" pmid="8118819">Birch et al., 1994</a>). <a href="#42" class="mim-tip-reference" title="Varley, J. M., McGown, G., Thorncroft, M., Santibanez-Koref, M. F., Kelsey, A. M., Tricker, K. J., Evans, D. G. R., Birch, J. M. <strong>Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families.</strong> Cancer Res. 57: 3245-3252, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9242456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9242456</a>]" pmid="9242456">Varley et al. (1997)</a> detected mutations in TP53 in approximately 70% of LFS and 20% of LFL families, when all exons, including noncoding regions, were sequenced. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9218725+8118819+3409256+9242456" 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="Chompret, A., Abel, A., Stoppa-Lyonnet, D., Brugieres, L., Pages, S., Feunteun, J., Bonaiti-Pellie, C. <strong>Sensitivity and predictive value of criteria for p53 germline mutation screening.</strong> J. Med. Genet. 38: 43-47, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11332399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11332399</a>] [<a href="https://doi.org/10.1136/jmg.38.1.43" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11332399">Chompret et al. (2001)</a> reported a family study of 2,691 children with a history of solid tumor before the age of 18. A subgroup of 239 children had in addition a family history of at least 1 cancer affecting a first- or second-degree relative before the age of 46 or multiple primary cancers in the proband. Among these 239, 211 had at least 1 first- or second-degree relative affected, 16 had at least 2 primary tumors, and 12 fulfilled both criteria. They performed genotyping of p53 and found mutations in 9 individuals from the first group, 1 in the second, and 5 in the third. <a href="#9" class="mim-tip-reference" title="Chompret, A., Abel, A., Stoppa-Lyonnet, D., Brugieres, L., Pages, S., Feunteun, J., Bonaiti-Pellie, C. <strong>Sensitivity and predictive value of criteria for p53 germline mutation screening.</strong> J. Med. Genet. 38: 43-47, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11332399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11332399</a>] [<a href="https://doi.org/10.1136/jmg.38.1.43" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11332399">Chompret et al. (2001)</a> calculated sensitivity and predictive value of p53 mutation testing using various degrees of stringency of selection criteria and concluded that p53 mutation testing should be considered in families where there is (1) a proband affected by a narrow spectrum cancer (sarcoma, brain tumor, breast cancer, adrenocortical tumor) before 36 years, and at least 1 first- or second-degree relative affected by a narrow spectrum tumor (other than breast cancer if the proband is affected by breast cancer) before the age of 46, or by multiple primary tumors; (2) a proband with multiple primary tumors, 2 of which belong to the narrow spectrum and the first of which occurred before 36 years, whatever the family history; (3) a proband with adrenocortical carcinoma, whatever the age of onset or family history. Using such criteria, they expected to find a mutation in 20% of cases and to miss 20% of mutations that would be detected by the least stringent criteria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11332399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Hwang, S.-J., Lozano, G., Amos, C. I., Strong, L. C. <strong>Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk.</strong> Am. J. Hum. Genet. 72: 975-983, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12610779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12610779</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12610779[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/10.1086/374567" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12610779">Hwang et al. (2003)</a> stated that germline mutations in the p53 gene had been identified in 50 to 70% of families with LFS. To characterize cancer risk in heterozygous p53 mutation carriers, they analyzed cancer incidence in 56 germline p53 mutation carriers and 3,201 noncarriers from 107 kindreds ascertained through patients with childhood soft tissue sarcoma. Members of these kindreds were systematically followed for more than 20 years for cancer incidence and their p53 gene status was evaluated. <a href="#20" class="mim-tip-reference" title="Hwang, S.-J., Lozano, G., Amos, C. I., Strong, L. C. <strong>Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk.</strong> Am. J. Hum. Genet. 72: 975-983, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12610779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12610779</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12610779[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/10.1086/374567" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12610779">Hwang et al. (2003)</a> identified 7 kindreds with germline p53 mutations that included missense and truncation mutation types. A significantly higher cancer risk was found in female carriers than in male carriers, a difference not explained by an excess of sex-specific cancer. The calculated standardized incidence ratio (SIR) showed that mutation carriers had a risk for all types of cancer that was much higher than that for the general population, whereas noncarriers had a risk for all types of cancer that was similar to that in the general population. The calculated SIRs showed a higher risk by more than 100-fold for sarcoma, female breast cancer, and hematologic malignancy for the p53 mutation carriers and agreed with the findings of an earlier segregation analysis based on the same cohort (<a href="#21" class="mim-tip-reference" title="Kleihues, P., Schauble, B., zur Hausen, A., Esteve, J., Ohgaki, H. <strong>Tumors associated with p53 germline mutations: a synopsis of 91 families.</strong> Am. J. Path. 150: 1-13, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9006316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9006316</a>]" pmid="9006316">Kleihues et al., 1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9006316+12610779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#43" class="mim-tip-reference" title="Varley, J. M. <strong>Germline TP53 mutations and Li-Fraumeni syndrome.</strong> Hum. Mutat. 21: 313-320, 2003. Erratum: Hum. Mutat. 21: 551 only, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12619118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12619118</a>] [<a href="https://doi.org/10.1002/humu.10185" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12619118">Varley (2003)</a> reviewed the findings of <a href="#3" class="mim-tip-reference" title="Birch, J. M., Alston, R. D., McNally, R. J. Q., Evans, D. G. R., Kelsey, A. M., Harris, M., Eden, O. B., Varley, J. M. <strong>Relative frequency and morphology of cancers in carriers of germline TP53 mutations.</strong> Oncogene 20: 4621-4628, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11498785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11498785</a>] [<a href="https://doi.org/10.1038/sj.onc.1204621" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11498785">Birch et al. (2001)</a>, who studied the distribution of cancers in carriers of germline TP53 mutations from 28 families in which all cancers were verified and the ages of all family members, affected and unaffected, were known. They found a highly significant difference from the expected cancer distribution in the general population. The tumors originally identified as being components of Li-Fraumeni syndrome were found to be strongly associated with a germline TP53 mutation, with the exception of leukemia, which was not found to be a major component. However, Wilms tumor and malignant phyllode tumors of the breast were found at significantly higher frequency. (Phyllode is a term applied to tumors that on section show a lobulated, leaf-like appearance.) The increased cancer risk was most marked at younger ages and decreased with age. The only common adult epithelial tumor apart from breast that could be found at an increased frequency was pancreas, with no increased risk of lung, ovary, bladder, bowel, or head and neck tumors. The latter observation was particularly interesting because somatic TP53 mutations are found in approximately 60% of sporadic tumors at these sites (<a href="#39" class="mim-tip-reference" title="Soussi, T., Dehouche, K., Beroud, C. <strong>p53 website and analysis of p53 gene mutations in human cancer: forging a link between epidemiology and carcinogenesis.</strong> Hum. Mutat. 15: 105-113, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10612830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10612830</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200001)15:1<105::AID-HUMU19>3.0.CO;2-G" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10612830">Soussi et al., 2000</a>). The tissue-cell specificity associated with inheritance of a germline TP53 mutation is very striking. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12619118+11498785+10612830" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Bendig, I., Mohr, N., Kramer, F., Weber, B. H. F. <strong>Identification of novel TP53 mutations in familial and sporadic cancer cases of German and Swiss origin.</strong> Cancer Genet. Cytogenet. 154: 22-26, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15381368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15381368</a>] [<a href="https://doi.org/10.1016/j.cancergencyto.2004.02.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15381368">Bendig et al. (2004)</a> sought to identify germline mutations in the TP53 gene in 5 index cases of German and Swiss origin with cancers typical of Li-Fraumeni syndrome. They identified 5 mutations, of which 3 were found in families with a strong history of LFS in several generations and 2 seemingly arose de novo. <a href="#2" class="mim-tip-reference" title="Bendig, I., Mohr, N., Kramer, F., Weber, B. H. F. <strong>Identification of novel TP53 mutations in familial and sporadic cancer cases of German and Swiss origin.</strong> Cancer Genet. Cytogenet. 154: 22-26, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15381368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15381368</a>] [<a href="https://doi.org/10.1016/j.cancergencyto.2004.02.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15381368">Bendig et al. (2004)</a> concluded that the frequent identification of de novo germline mutations emphasizes the importance of mutation analyses of the TP53 gene in young patients with malignancies typical for LFS but without a positive family history of this tumor syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15381368" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#45" class="mim-tip-reference" title="Wang, P., Ma, W., Park, J.-Y., Celi, F. S., Arena, R., Choi, J. W., Ali, Q. A., Tripodi, D. J., Zhuang, J., Lago, C. U., Strong, L. C., Talagala, S. L., Balaban, R. S., Kang, J.-G., Hwang, P. M. <strong>Increased oxidative metabolism in the Li-Fraumeni syndrome.</strong> New Eng. J. Med. 368: 1027-1032, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23484829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23484829</a>] [<a href="https://doi.org/10.1056/NEJMoa1214091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23484829">Wang et al. (2013)</a> reported on members of families with Li-Fraumeni syndrome who carried germline mutations in the TP53 gene. As compared with family members who are not carriers and with healthy volunteers, family members with these mutations have increased oxidative phosphorylation of skeletal muscle. Basic experimental studies of tissue samples from patients with the Li-Fraumeni syndrome and a mouse model of the syndrome supported this in vivo finding of increased mitochondrial function. <a href="#45" class="mim-tip-reference" title="Wang, P., Ma, W., Park, J.-Y., Celi, F. S., Arena, R., Choi, J. W., Ali, Q. A., Tripodi, D. J., Zhuang, J., Lago, C. U., Strong, L. C., Talagala, S. L., Balaban, R. S., Kang, J.-G., Hwang, P. M. <strong>Increased oxidative metabolism in the Li-Fraumeni syndrome.</strong> New Eng. J. Med. 368: 1027-1032, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23484829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23484829</a>] [<a href="https://doi.org/10.1056/NEJMoa1214091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23484829">Wang et al. (2013)</a> concluded that their results suggested that p53 regulates bioenergetic homeostasis in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23484829" 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>Other Genetic Abnormalities</em></strong></p><p>
|
|
<a href="#38" class="mim-tip-reference" title="Shlien, A., Tabori, U., Marshall, C. R., Pienkowska, M., Feuk, L., Novokmet, A., Nanda, S., Druker, H., Scherer, S. W., Malkin, D. <strong>Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome.</strong> Proc. Nat. Acad. Sci. 105: 11264-11269, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18685109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18685109</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18685109[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0802970105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18685109">Shlien et al. (2008)</a> found that patients with TP53 mutations had significantly higher numbers of germline copy number variation (CNV) compared to controls. A microarray analysis counting CNVs on autosomal chromosomes comprising of 2 or more SNP probes identified 3,884 CNVs in genomic DNA from 770 healthy individuals. The median number of CNVs detected per control individual was 3, with 75% of the population having 4 or fewer CNVs. In individuals from 11 LFS families with TP53 mutations, the CNV mean was 12.19 per person, with 75% having 10 or fewer CNVs. The difference from controls was statistically significant (p = 0.01). The majority of specific CNVs observed in LFS families were acquired and not found in either parent. There was also a correlation between increased CNV number and cancer development among the LFS families, and analysis of tumor samples showed somatic increases in CNV. <a href="#38" class="mim-tip-reference" title="Shlien, A., Tabori, U., Marshall, C. R., Pienkowska, M., Feuk, L., Novokmet, A., Nanda, S., Druker, H., Scherer, S. W., Malkin, D. <strong>Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome.</strong> Proc. Nat. Acad. Sci. 105: 11264-11269, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18685109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18685109</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18685109[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0802970105" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18685109">Shlien et al. (2008)</a> suggested that CNVs represent regions of genomic instability and early neoplastic transformation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18685109" 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="#37" class="mim-tip-reference" title="Shlien, A., Baskin, B., Achatz, M. I. W., Stavropoulos, D. J., Nichols, K. E., Hudgins, L., Morel, C. F., Adam, M. P., Zhukova, N., Rotin, L., Novokmet, A., Druker, H., Shago, M., Ray, P. N., Hainaut, P., Malkin, D. <strong>A common molecular mechanism underlies two phenotypically distinct 17p13.1 microdeletion syndromes.</strong> Am. J. Hum. Genet. 87: 631-642, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21056402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21056402</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21056402[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2010.10.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21056402">Shlien et al. (2010)</a> screened 4,524 patients with diverse clinical phenotypes for DNA dosage changes via array CGH or MLPA and identified 8 probands with a microdeletion on chromosome 17p13.1, at the TP53 (<a href="/entry/191170">191170</a>) locus. In 4 of the patients, who had childhood cancer and pedigrees consistent with Li-Fraumeni syndrome, deletions limited to the TP53 gene were found which deleted between 1 and 10 of the 11 exons. Another 4 patients, with a noncancer neurocognitive phenotype (<a href="/entry/613776">613776</a>), had larger deletions at 17p13.1, encompassing the entire TP53 gene and 26 to 85 other fully deleted genes. <a href="#37" class="mim-tip-reference" title="Shlien, A., Baskin, B., Achatz, M. I. W., Stavropoulos, D. J., Nichols, K. E., Hudgins, L., Morel, C. F., Adam, M. P., Zhukova, N., Rotin, L., Novokmet, A., Druker, H., Shago, M., Ray, P. N., Hainaut, P., Malkin, D. <strong>A common molecular mechanism underlies two phenotypically distinct 17p13.1 microdeletion syndromes.</strong> Am. J. Hum. Genet. 87: 631-642, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21056402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21056402</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21056402[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2010.10.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21056402">Shlien et al. (2010)</a> demonstrated that mRNA expression levels of TP53 and TP53-dependent genes were altered in patients with partial, but not complete, deletions, which was consistent with mutant TP53-initiated tumorigenesis in the former group but not in the latter. The authors stated that their data supported a model in which partial deletions lead to the expression of a truncated protein, rather than the complete absence of it due to nonsense-mediated decay. Truncated and wildtype protein would oligomerize to form a defective TP53 tetramer, leading to a dominant-negative or gain-of-function effect similar to that observed with certain missense mutations, resulting in inhibition of wildtype TP53 function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21056402" 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="genotypePhenotypeCorrelations" class="mim-anchor"></a>
|
|
<h4 href="#mimGenotypePhenotypeCorrelationsFold" id="mimGenotypePhenotypeCorrelationsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimGenotypePhenotypeCorrelationsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimGenotypePhenotypeCorrelationsFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#33" class="mim-tip-reference" title="Olivier, M. Goldgar, D. E., Sodha, N., Ohgaki, H., Kleihues, P., Hainaut, P., Eeles, R. A. <strong>Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype.</strong> Cancer Res. 63: 6643-6650, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14583457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14583457</a>]" pmid="14583457">Olivier et al. (2003)</a> described a database for collecting information on families carrying a germline mutation in the TP53 gene and on families affected with Li-Fraumeni syndromes, both Li-Fraumeni and Li-Fraumeni-like syndromes. Data from the published literature was included. They described analysis of 265 families/individuals with LFS/LFL. In classic LFS families with a germline TP53 mutation (83 families), the mean age of onset of breast cancer was significantly lower than in LFS families (16 families) without a TP53 mutation (34.6 vs. 42.5 years; P = 0.0035). In individuals with a TP53 mutation, a correlation between the genotype and phenotype was found: brain tumors were associated with missense TP53 mutations located in the DNA-binding loop that contact the minor groove of DNA (P = 0.01), whereas adrenal gland carcinomas were associated with missense mutations located in the loops opposing the protein-DNA contact surface (P = 0.003). Finally, mutations likely to result in a null phenotype (absence of the protein or loss of function) were associated with earlier onset brain tumors (P = 0.004). These observations were considered to have clinical implications for genetic testing and tumor surveillance in LFS/LFL families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14583457" 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="Capponcelli, S., Pedrini, E., Cerone, M. A., Corti, V., Fontanesi, S., Alessio, M., Bachi, A., Soddu, S., Ribatti, D., Picci, P., Helman, L. J., Cantelli-Forti, G., Sangiorgi, L. <strong>Evaluation of the molecular mechanisms involved in the gain of function of a Li-Fraumeni TP53 mutation.</strong> Hum. Mutat. 26: 94-103, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15977174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15977174</a>] [<a href="https://doi.org/10.1002/humu.20192" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15977174">Capponcelli et al. (2005)</a> identified a mutation in the TP53 gene (Y220S; <a href="/entry/191170#0039">191170.0039</a>) in a mother and her 3 children with Li-Fraumeni syndrome. All affected family members had a very aggressive clinical phenotype associated with resistance to doxorubicin and early death from cancer. In vitro studies showed that the mutation conferred increased cellular resistance to doxorubicin treatment, perhaps by inducing expression of peroxiredoxin II (PRDX2; <a href="/entry/600538">600538</a>) and thioredoxin (TXN; <a href="/entry/187700">187700</a>), both of which reduce reactive oxygen species. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15977174" 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="otherFeatures" class="mim-anchor"></a>
|
|
<h4 href="#mimOtherFeaturesFold" id="mimOtherFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimOtherFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Other Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimOtherFeaturesFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Choriocarcinoma</em></strong></p><p>
|
|
<a href="#34" class="mim-tip-reference" title="Patrier-Sallebert, S., Bougeard, G., Baert-Desurmont, S., Lamy, A., Flaman, J.-M., Mansuy, L., Bronner, M., Lasset, C., Brugieres, L., Golfier, F., Frebourg, T. <strong>Transmission of germline TP53 mutations from male carriers to female partners.</strong> J. Med. Genet. 52: 145-146, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25612911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25612911</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102853" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25612911">Patrier-Sallebert et al. (2015)</a> reported a gestational choriocarcinoma (CC) that developed in a female partner of a male patient with LFS; the CC carried a germline TP53 (<a href="/entry/191170">191170</a>) mutation initially detected in this LFS patient. The authors then identified 78 fathers who were carriers of a germline TP53 mutation. Among the 213 corresponding pregnancies, <a href="#34" class="mim-tip-reference" title="Patrier-Sallebert, S., Bougeard, G., Baert-Desurmont, S., Lamy, A., Flaman, J.-M., Mansuy, L., Bronner, M., Lasset, C., Brugieres, L., Golfier, F., Frebourg, T. <strong>Transmission of germline TP53 mutations from male carriers to female partners.</strong> J. Med. Genet. 52: 145-146, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25612911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25612911</a>] [<a href="https://doi.org/10.1136/jmedgenet-2014-102853" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25612911">Patrier-Sallebert et al. (2015)</a> found 2 other cases of gestational CC in the female partners, and estimated that gestational CC occurs in approximately 1% of the deliveries in female partners of TP53 mutation carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25612911" 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="heterogeneity" class="mim-anchor"></a>
|
|
<h4 href="#mimHeterogeneityFold" id="mimHeterogeneityToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimHeterogeneityToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>Heterogeneity</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimHeterogeneityFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p>Mutations in p53 had not been detected in approximately 30% of LFS families. To address the possibility either that TP53 mutations were missed or that another predisposing gene is altered in LFS, <a href="#13" class="mim-tip-reference" title="Evans, S. C., Mims, B., McMasters, K. M., Foster, C. J., deAndrade, M., Amos, C. I., Strong, L. C., Lozano, G. <strong>Exclusion of a p53 germline mutation in a classic Li-Fraumeni syndrome family.</strong> Hum. Genet. 102: 681-686, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9703430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9703430</a>] [<a href="https://doi.org/10.1007/s004390050761" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9703430">Evans et al. (1998)</a> used a variety of methods to determine the TP53 status in a large LFS kindred. A transcriptional activation assay on exons 4 to 10 of TP53 excluded a mutation within the DNA-binding domain. SSCP analysis, using intronic primers and sequencing of all the coding exons and intron/exon junctions, also yielded no mutations. Finally, linkage analysis excluded potential mutations in the noncoding regions of TP53. The family had been ascertained through systematic surveys of cancer in relatives of 382 childhood osteosarcoma patients. Classic LFS was defined as the diagnosis of a sarcoma in an individual before 45 years of age, having 2 first-degree relatives with cancer before the age of 45 years. In the LFS kindred studied, in addition to osteosarcoma in the proband, a sister had osteosarcoma and the mother had breast cancer before the age of 45 years. There was also lung cancer in the family as well as cancers of the ovary, thyroid, tongue, and kidney. Thirteen members were affected in 7 sibships in 3 generations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9703430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Lynch, H. T., McComb, R. D., Osborn, N. K., Wolpert, P. A., Lynch, J. F., Wszolek, Z. K., Sidransky, D., Steg, R. E. <strong>Predominance of brain tumors in an extended Li-Fraumeni (SBLA) kindred, including a case of Sturge-Weber syndrome.</strong> Cancer 88: 433-439, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10640978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10640978</a>] [<a href="https://doi.org/10.1002/(sici)1097-0142(20000115)88:2<433::aid-cncr26>3.0.co;2-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10640978">Lynch et al. (2000)</a> reported extensive follow-up of the family described by <a href="#29" class="mim-tip-reference" title="Lynch, H. T., Mulcahy, G. M., Harris, R. E., Guirgis, H. A., Lynch, J. F. <strong>Genetic and pathologic findings in a kindred with hereditary sarcoma breast cancer, brain tumors, leukemia, lung, laryngeal, and adrenal cortical carcinoma.</strong> Cancer 41: 2055-2064, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/647640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">647640</a>] [<a href="https://doi.org/10.1002/1097-0142(197805)41:5<2055::aid-cncr2820410554>3.0.co;2-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="647640">Lynch et al. (1978)</a>; a remarkable excess of brain tumors became evident in the update. One patient in the direct genetic lineage had a rhabdomyosarcoma of the eyelid at age 29 months and, at age 14 years, was diagnosed with lymphoblastic lymphoma/acute lymphoblastic leukemia. This same patient also had Sturge-Weber syndrome (<a href="/entry/185300">185300</a>), which seemingly had not previously been identified in Li-Fraumeni syndrome. No p53 germline mutation was identified in any affected members of this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10640978+647640" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a large pedigree with tumors suggestive of a Li-Fraumeni-like syndrome, in which mutation in the TP53 gene had been excluded, <a href="#11" class="mim-tip-reference" title="Evans, D. G., Wu, C. L., Birch, J. M. <strong>BRCA2: a cause of Li-Fraumeni-like syndrome. (Letter)</strong> J. Med. Genet. 45: 62-63, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18178637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18178637</a>] [<a href="https://doi.org/10.1136/jmg.2007.054494" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18178637">Evans et al. (2008)</a> identified a deletion of exons 14 to 16 in the BRCA2 gene by multiplex ligation-dependent probe amplification (MLPA) assay. Noting that other BRCA2 families have been reported with LFS spectrum sarcomas, the authors concluded that BRCA2 clearly accounts for a proportion of LFS/LFL families negative for TP53 mutations, but that it is likely that TP53 is the only LF-specific gene and that TP53-negative families are due to mutations in a variety of other, mostly known, genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18178637" 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>Exclusion Studies</em></strong></p><p>
|
|
In a Turkish family with Li-Fraumeni syndrome, <a href="#17" class="mim-tip-reference" title="Guran, S., Tunca, Y., Imirzalioglu, N. <strong>Hereditary TP53 codon 292 and somatic P16(INK4A) codon 94 mutations in a Li-Fraumeni syndrome family.</strong> Cancer Genet. Cytogenet. 113: 145-151, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10484981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10484981</a>] [<a href="https://doi.org/10.1016/s0165-4608(98)00276-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10484981">Guran et al. (1999)</a> demonstrated that the propositus with seminoma and his daughter with medulloblastoma had a hereditary TP53 mutation, lys292 to ile (K292I; <a href="/entry/191170#0034">191170.0034</a>), but also in analyses of tumor tissues had an ala94-to-glu missense mutation of the CDKN2A gene. Full blood analysis in the 2 cases revealed no CDKN2A mutation. This was the first time that a mutation in CDKN2A had been observed in Li-Fraumeni syndrome. <a href="#7" class="mim-tip-reference" title="Burt, E. C., McGown, G., Thorncroft, M., James, L. A., Birch, J. M., Varley, J. M. <strong>Exclusion of the genes CDKN2 and PTEN as causative gene defects in Li-Fraumeni syndrome.</strong> Brit. J. Cancer 80: 9-10, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10389970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10389970</a>] [<a href="https://doi.org/10.1038/sj.bjc.6690313" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10389970">Burt et al. (1999)</a> excluded CDKN2A (<a href="/entry/600160">600160</a>) on chromosome 9 and PTEN (<a href="/entry/601728">601728</a>) on chromosome 10 as the cause of either LFS or LFL. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10389970+10484981" 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>The heterogeneity in the tumor spectrum and latency in patients with LFS due to inherited mutations in p53 suggest risk modifiers at loci other than the major gene. <a href="#12" class="mim-tip-reference" title="Evans, S. C., Liang, M., Amos, C., Gu, X., Lozano, G. <strong>A novel genetic modifier of p53, mop1, results in embryonic lethality.</strong> Mammalian Genome 15: 415-423, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15181534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15181534</a>] [<a href="https://doi.org/10.1007/s00335-004-2327-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15181534">Evans et al. (2004)</a> developed a mouse model to investigate these risk modifiers. Inbred CE/J mice, which succumbed to multiple types of tumors similar to those found in LFS, were crossed with the p53 null mouse. In this cross, the authors found evidence for a genetic modifier of p53, Mop1, based on an unexpected mix of genotypes in the F2 progeny. A model in which a recessive CE/J allele in combination with p53 heterozygosity or homozygosity results in lethality most closely fitted the data. Using simple sequence length polymorphism analysis of the entire genome, <a href="#12" class="mim-tip-reference" title="Evans, S. C., Liang, M., Amos, C., Gu, X., Lozano, G. <strong>A novel genetic modifier of p53, mop1, results in embryonic lethality.</strong> Mammalian Genome 15: 415-423, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15181534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15181534</a>] [<a href="https://doi.org/10.1007/s00335-004-2327-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15181534">Evans et al. (2004)</a> identified a putative chromosomal region for this modifier of p53 on mouse chromosome 11 centromeric to p53. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15181534" 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="history" class="mim-anchor"></a>
|
|
<h4 href="#mimHistoryFold" id="mimHistoryToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimHistoryToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<div id="mimHistoryFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<p><a href="#1" class="mim-tip-reference" title="Bachinski, L. L., Olufemi, S.-E., Zhou, X., Wu, C.-C., Yip, L., Shete, S., Lozano, G., Amos, C. I., Strong, L. C., Krahe, R. <strong>Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23.</strong> Cancer Res. 65: 427-431, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15695383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15695383</a>]" pmid="15695383">Bachinski et al. (2005)</a> studied a series of LFS kindreds with no p53 or CHEK2 (<a href="/entry/604373">604373</a>) mutations. Using a genomewide scan for linkage with complementing parametric and nonparametric analysis methods, they mapped a novel locus, previously designated Li-Fraumeni syndrome-3 (LFS3), to a 4-cM region on chromosome 1q23. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15695383" 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="seeAlso" class="mim-anchor"></a>
|
|
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span class="mim-font">
|
|
<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
|
|
<span class="mim-text-font">
|
|
<a href="#Li1969" class="mim-tip-reference" title="Li, F. P., Fraumeni, J. F. <strong>Rhabdomyosarcoma in children: an epidemiologic study and identification of a familial cancer syndrome.</strong> J. Nat. Cancer Inst. 43: 1365-1373, 1969.">Li and Fraumeni (1969)</a>; <a href="#Li1975" class="mim-tip-reference" title="Li, F. P., Fraumeni, J. F., Jr. <strong>Familial breast cancer, soft-tissue sarcomas, and other neoplasms. (Letter)</strong> Ann. Intern. Med. 83: 833-834, 1975.">Li and Fraumeni (1975)</a>; <a href="#Lynch1985" class="mim-tip-reference" title="Lynch, H. T., Katz, D. A., Bogard, P. J., Lynch, J. F. <strong>The sarcoma, breast cancer, lung cancer, and adrenocortical carcinoma syndrome revisited.</strong> Am. J. Dis. Child. 139: 134-136, 1985.">Lynch et al. (1985)</a>
|
|
</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="Bachinski2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bachinski, L. L., Olufemi, S.-E., Zhou, X., Wu, C.-C., Yip, L., Shete, S., Lozano, G., Amos, C. I., Strong, L. C., Krahe, R.
|
|
<strong>Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23.</strong>
|
|
Cancer Res. 65: 427-431, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15695383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15695383</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15695383" 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="2" class="mim-anchor"></a>
|
|
<a id="Bendig2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bendig, I., Mohr, N., Kramer, F., Weber, B. H. F.
|
|
<strong>Identification of novel TP53 mutations in familial and sporadic cancer cases of German and Swiss origin.</strong>
|
|
Cancer Genet. Cytogenet. 154: 22-26, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15381368/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15381368</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15381368" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.cancergencyto.2004.02.017" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Birch2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Birch, J. M., Alston, R. D., McNally, R. J. Q., Evans, D. G. R., Kelsey, A. M., Harris, M., Eden, O. B., Varley, J. M.
|
|
<strong>Relative frequency and morphology of cancers in carriers of germline TP53 mutations.</strong>
|
|
Oncogene 20: 4621-4628, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11498785/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11498785</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11498785" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.onc.1204621" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Birch1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Birch, J. M., Hartley, A. L., Blair, V., Kelsey, A. M., Harris, M., Teare, M. D., Jones, P. H. M.
|
|
<strong>Identification of factors associated with high breast cancer risk in the mothers of children with soft tissue sarcoma.</strong>
|
|
J. Clin. Oncol. 8: 583-590, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2313328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2313328</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2313328" 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.1990.8.4.583" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Birch1984" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Birch, J. M., Hartley, A. L., Marsden, H. B., Harris, M., Swindell, R.
|
|
<strong>Excess risk of breast cancer in the mothers of children with soft tissue sarcomas.</strong>
|
|
Brit. J. Cancer 49: 325-331, 1984.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6704308/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6704308</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6704308" 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/bjc.1984.51" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Birch1994" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Birch, J. M., Hartley, A. L., Tricker, K. J., Prosser, J., Condie, A., Kelsey, A. M., Harris, M., Jones, P. H. M., Binchy, A., Crowther, D., Craft, A. W., Eden, O. B., Evans, D. G. R., Thompson, E., Mann, J. R., Martin, J., Mitchell, E. L. D., Santibanez-Koref, M. F.
|
|
<strong>Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.</strong>
|
|
Cancer Res. 54: 1298-1304, 1994.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8118819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8118819</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8118819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Burt1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Burt, E. C., McGown, G., Thorncroft, M., James, L. A., Birch, J. M., Varley, J. M.
|
|
<strong>Exclusion of the genes CDKN2 and PTEN as causative gene defects in Li-Fraumeni syndrome.</strong>
|
|
Brit. J. Cancer 80: 9-10, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10389970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10389970</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10389970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.bjc.6690313" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Capponcelli2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Capponcelli, S., Pedrini, E., Cerone, M. A., Corti, V., Fontanesi, S., Alessio, M., Bachi, A., Soddu, S., Ribatti, D., Picci, P., Helman, L. J., Cantelli-Forti, G., Sangiorgi, L.
|
|
<strong>Evaluation of the molecular mechanisms involved in the gain of function of a Li-Fraumeni TP53 mutation.</strong>
|
|
Hum. Mutat. 26: 94-103, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15977174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15977174</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15977174" 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/humu.20192" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Chompret2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chompret, A., Abel, A., Stoppa-Lyonnet, D., Brugieres, L., Pages, S., Feunteun, J., Bonaiti-Pellie, C.
|
|
<strong>Sensitivity and predictive value of criteria for p53 germline mutation screening.</strong>
|
|
J. Med. Genet. 38: 43-47, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11332399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11332399</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11332399" 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.38.1.43" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Eeles1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Eeles, R. A.
|
|
<strong>Germline mutations in the TP53 gene.</strong>
|
|
Cancer Surv. 25: 101-124, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8718514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8718514</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8718514" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Evans2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Evans, D. G., Wu, C. L., Birch, J. M.
|
|
<strong>BRCA2: a cause of Li-Fraumeni-like syndrome. (Letter)</strong>
|
|
J. Med. Genet. 45: 62-63, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18178637/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18178637</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18178637" 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.2007.054494" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="Evans2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Evans, S. C., Liang, M., Amos, C., Gu, X., Lozano, G.
|
|
<strong>A novel genetic modifier of p53, mop1, results in embryonic lethality.</strong>
|
|
Mammalian Genome 15: 415-423, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15181534/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15181534</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15181534" 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/s00335-004-2327-y" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Evans1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Evans, S. C., Mims, B., McMasters, K. M., Foster, C. J., deAndrade, M., Amos, C. I., Strong, L. C., Lozano, G.
|
|
<strong>Exclusion of a p53 germline mutation in a classic Li-Fraumeni syndrome family.</strong>
|
|
Hum. Genet. 102: 681-686, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9703430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9703430</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9703430" 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/s004390050761" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Fraumeni1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fraumeni, J. F., Jr., Wertelecki, W., Blattner, W. A., Jensen, R. D., Leventhal, B. G.
|
|
<strong>Varied manifestations of a familial lymphoproliferative disorder.</strong>
|
|
Am. J. Med. 59: 145-151, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/806230/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">806230</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=806230" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0002-9343(75)90333-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Frebourg1995" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Frebourg, T., Barbier, N., Yan, Y., Garber, J. E., Dreyfus, M., Fraumeni, J., Jr., Li, F. P., Friend, S. H.
|
|
<strong>Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome.</strong>
|
|
Am. J. Hum. Genet. 56: 608-615, 1995.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7887414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7887414</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7887414" 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="16" class="mim-anchor"></a>
|
|
<a id="Gonzalez2009" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gonzalez, K. D., Buzin, C. H., Noltner, K. A., Gu, D., Li, W., Malkin, D., Sommer, S. S.
|
|
<strong>High frequency of de novo mutations in Li-Fraumeni syndrome.</strong>
|
|
J. Med. Genet. 46: 689-693, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19556618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19556618</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19556618" 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.2008.058958" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Guran1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Guran, S., Tunca, Y., Imirzalioglu, N.
|
|
<strong>Hereditary TP53 codon 292 and somatic P16(INK4A) codon 94 mutations in a Li-Fraumeni syndrome family.</strong>
|
|
Cancer Genet. Cytogenet. 113: 145-151, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10484981/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10484981</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10484981" 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/s0165-4608(98)00276-3" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Hartley1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hartley, A. L., Birch, J. M., Marsden, H. B., Harris, M.
|
|
<strong>Malignant melanoma in families of children with osteosarcoma, chondrosarcoma, and adrenal cortical carcinoma.</strong>
|
|
J. Med. Genet. 24: 664-668, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3480957/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3480957</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3480957" 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.24.11.664" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Hisada1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hisada, M., Garber, J. E., Fung, C. Y., Fraumeni, J. F., Jr., Li, F. P.
|
|
<strong>Multiple primary cancers in families with Li-Fraumeni syndrome.</strong>
|
|
J. Nat. Cancer Inst. 90: 606-611, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9554443/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9554443</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9554443" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/jnci/90.8.606" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Hwang2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hwang, S.-J., Lozano, G., Amos, C. I., Strong, L. C.
|
|
<strong>Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk.</strong>
|
|
Am. J. Hum. Genet. 72: 975-983, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12610779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12610779</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12610779[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=12610779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/374567" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Kleihues1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kleihues, P., Schauble, B., zur Hausen, A., Esteve, J., Ohgaki, H.
|
|
<strong>Tumors associated with p53 germline mutations: a synopsis of 91 families.</strong>
|
|
Am. J. Path. 150: 1-13, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9006316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9006316</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9006316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Li1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, F. P., Fraumeni, J. F., Jr.
|
|
<strong>Soft-tissue sarcomas, breast cancer, and other neoplasms: a familial syndrome?</strong>
|
|
Ann. Intern. Med. 71: 747-752, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5360287/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5360287</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5360287" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-71-4-747" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Li1975" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, F. P., Fraumeni, J. F., Jr.
|
|
<strong>Familial breast cancer, soft-tissue sarcomas, and other neoplasms. (Letter)</strong>
|
|
Ann. Intern. Med. 83: 833-834, 1975.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1200533/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1200533</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1200533" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.7326/0003-4819-83-6-833_2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Li1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, F. P., Fraumeni, J. F., Jr.
|
|
<strong>Prospective study of a family cancer syndrome.</strong>
|
|
JAMA 247: 2692-2694, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7077763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7077763</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7077763" 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="25" class="mim-anchor"></a>
|
|
<a id="Li1969" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, F. P., Fraumeni, J. F.
|
|
<strong>Rhabdomyosarcoma in children: an epidemiologic study and identification of a familial cancer syndrome.</strong>
|
|
J. Nat. Cancer Inst. 43: 1365-1373, 1969.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5396222/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5396222</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5396222" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Li1988" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Li, F. P., Fraumeni, J. R., Jr., Mulvihill, J. J., Blattner, W. A., Dreyfus, M. G., Tucker, M. A., Miller, R. W.
|
|
<strong>A cancer family syndrome in twenty-four kindreds.</strong>
|
|
Cancer Res. 48: 5358-5362, 1988.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3409256/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3409256</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3409256" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Lynch1985" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lynch, H. T., Katz, D. A., Bogard, P. J., Lynch, J. F.
|
|
<strong>The sarcoma, breast cancer, lung cancer, and adrenocortical carcinoma syndrome revisited.</strong>
|
|
Am. J. Dis. Child. 139: 134-136, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3976585/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3976585</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3976585" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1001/archpedi.1985.02140040032020" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Lynch2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lynch, H. T., McComb, R. D., Osborn, N. K., Wolpert, P. A., Lynch, J. F., Wszolek, Z. K., Sidransky, D., Steg, R. E.
|
|
<strong>Predominance of brain tumors in an extended Li-Fraumeni (SBLA) kindred, including a case of Sturge-Weber syndrome.</strong>
|
|
Cancer 88: 433-439, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10640978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10640978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10640978" 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/(sici)1097-0142(20000115)88:2<433::aid-cncr26>3.0.co;2-0" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Lynch1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Lynch, H. T., Mulcahy, G. M., Harris, R. E., Guirgis, H. A., Lynch, J. F.
|
|
<strong>Genetic and pathologic findings in a kindred with hereditary sarcoma breast cancer, brain tumors, leukemia, lung, laryngeal, and adrenal cortical carcinoma.</strong>
|
|
Cancer 41: 2055-2064, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/647640/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">647640</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=647640" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1097-0142(197805)41:5<2055::aid-cncr2820410554>3.0.co;2-x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Malkin1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Jr., Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., Friend, S. H.
|
|
<strong>Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.</strong>
|
|
Science 250: 1233-1238, 1990. Note: Erratum: Science 259: 878 only, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1978757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1978757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1978757" 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.1978757" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Masciari2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Masciari, S., Dewanwala, A., Stoffel, E. M., Lauwers, G. Y., Zheng, H., Achatz, M. I., Riegert-Johnson, D., Foretova, L., Silva, E. M., Digianni, L., Verselis, S. J., Schneider, K., Li, F. P., Fraumeni, J., Garber, J. E., Syngal, S.
|
|
<strong>Gastric cancer in individuals with Li-Fraumeni syndrome.</strong>
|
|
Genet. Med. 13: 651-657, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21552135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21552135</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21552135[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=21552135" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1097/GIM.0b013e31821628b6" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Mulvihill1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mulvihill, J. J.
|
|
<strong>Personal Communication.</strong>
|
|
Bethesda, Md. 6/11/1982.
|
|
|
|
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Olivier2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Olivier, M. Goldgar, D. E., Sodha, N., Ohgaki, H., Kleihues, P., Hainaut, P., Eeles, R. A.
|
|
<strong>Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype.</strong>
|
|
Cancer Res. 63: 6643-6650, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14583457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14583457</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14583457" 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="34" class="mim-anchor"></a>
|
|
<a id="Patrier-Sallebert2015" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Patrier-Sallebert, S., Bougeard, G., Baert-Desurmont, S., Lamy, A., Flaman, J.-M., Mansuy, L., Bronner, M., Lasset, C., Brugieres, L., Golfier, F., Frebourg, T.
|
|
<strong>Transmission of germline TP53 mutations from male carriers to female partners.</strong>
|
|
J. Med. Genet. 52: 145-146, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25612911/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25612911</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25612911" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1136/jmedgenet-2014-102853" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Pearson1982" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pearson, A. D. J., Craft, A. W., Ratcliffe, J. M., Birch, J. M., Morris-Jones, P., Roberts, D. F.
|
|
<strong>Two families with the Li-Fraumeni cancer family syndrome.</strong>
|
|
J. Med. Genet. 19: 362-365, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6958872/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6958872</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6958872" 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.19.5.362" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Shete2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shete, S., Amos, C. I., Hwang, S.-J., Strong, L. C.
|
|
<strong>Individual-specific liability groups in genetic linkage, with applications to kindreds with Li-Fraumeni syndrome.</strong>
|
|
Am. J. Hum. Genet. 70: 813-817, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11822026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11822026</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11822026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1086/339370" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Shlien2010" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shlien, A., Baskin, B., Achatz, M. I. W., Stavropoulos, D. J., Nichols, K. E., Hudgins, L., Morel, C. F., Adam, M. P., Zhukova, N., Rotin, L., Novokmet, A., Druker, H., Shago, M., Ray, P. N., Hainaut, P., Malkin, D.
|
|
<strong>A common molecular mechanism underlies two phenotypically distinct 17p13.1 microdeletion syndromes.</strong>
|
|
Am. J. Hum. Genet. 87: 631-642, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21056402/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21056402</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21056402[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=21056402" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajhg.2010.10.007" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Shlien2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shlien, A., Tabori, U., Marshall, C. R., Pienkowska, M., Feuk, L., Novokmet, A., Nanda, S., Druker, H., Scherer, S. W., Malkin, D.
|
|
<strong>Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 11264-11269, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18685109/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18685109</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18685109[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=18685109" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.0802970105" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Soussi2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Soussi, T., Dehouche, K., Beroud, C.
|
|
<strong>p53 website and analysis of p53 gene mutations in human cancer: forging a link between epidemiology and carcinogenesis.</strong>
|
|
Hum. Mutat. 15: 105-113, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10612830/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10612830</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10612830" 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/(SICI)1098-1004(200001)15:1<105::AID-HUMU19>3.0.CO;2-G" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Strong1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Strong, L. C., Stine, M., Norsted, T. L.
|
|
<strong>Cancer in survivors of childhood soft tissue sarcoma and their relatives.</strong>
|
|
J. Nat. Cancer Inst. 79: 1213-1220, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3480372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3480372</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3480372" 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="41" class="mim-anchor"></a>
|
|
<a id="Varley1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Varley, J. M., Evans, D. G. R., Birch, J. M.
|
|
<strong>Li-Fraumeni syndrome: a molecular and clinical review.</strong>
|
|
Brit. J. Cancer 76: 1-14, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9218725/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9218725</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9218725" 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/bjc.1997.328" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Varley1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Varley, J. M., McGown, G., Thorncroft, M., Santibanez-Koref, M. F., Kelsey, A. M., Tricker, K. J., Evans, D. G. R., Birch, J. M.
|
|
<strong>Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families.</strong>
|
|
Cancer Res. 57: 3245-3252, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9242456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9242456</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9242456" 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="43" class="mim-anchor"></a>
|
|
<a id="Varley2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Varley, J. M.
|
|
<strong>Germline TP53 mutations and Li-Fraumeni syndrome.</strong>
|
|
Hum. Mutat. 21: 313-320, 2003. Erratum: Hum. Mutat. 21: 551 only, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12619118/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12619118</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12619118" 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/humu.10185" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Villani2016" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Villani, A., Shore, A., Wasserman, J. D., Stephens, D., Kim, R. H., Druker, H., Gallinger, B., Naumer, A., Kohlmann, W., Novokmet, A., Tabori, U., Tijerin, M., Greer, M.-L. C., Finlay, J. L., Schiffman, J. D., Malkin, D.
|
|
<strong>Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study.</strong>
|
|
Lancet Oncol. 17: 1295-1305, 2016.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27501770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27501770</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27501770" 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/S1470-2045(16)30249-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Wang2013" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Wang, P., Ma, W., Park, J.-Y., Celi, F. S., Arena, R., Choi, J. W., Ali, Q. A., Tripodi, D. J., Zhuang, J., Lago, C. U., Strong, L. C., Talagala, S. L., Balaban, R. S., Kang, J.-G., Hwang, P. M.
|
|
<strong>Increased oxidative metabolism in the Li-Fraumeni syndrome.</strong>
|
|
New Eng. J. Med. 368: 1027-1032, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23484829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23484829</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23484829" 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/NEJMoa1214091" 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 : 11/22/2017
|
|
</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 : 7/9/2015<br>Ada Hamosh - updated : 4/1/2013<br>Ada Hamosh - updated : 8/19/2011<br>Marla J. F. O'Neill - updated : 2/24/2011<br>Cassandra L. Kniffin - updated : 1/25/2010<br>Cassandra L. Kniffin - updated : 4/13/2009<br>Marla J. F. O'Neill - updated : 11/6/2008<br>Matthew B. Gross - updated : 2/1/2008<br>Victor A. McKusick - updated : 1/31/2007<br>Cassandra L. Kniffin - updated : 8/11/2006<br>Victor A. McKusick - updated : 3/17/2005<br>Victor A. McKusick - updated : 1/31/2005<br>Victor A. McKusick - updated : 8/24/2004<br>Victor A. McKusick - updated : 2/2/2004<br>Victor A. McKusick - updated : 1/21/2004<br>Victor A. McKusick - updated : 12/23/2003<br>Victor A. McKusick - updated : 4/10/2003<br>Victor A. McKusick - updated : 3/22/2002<br>Michael J. Wright - updated : 1/30/2001<br>Victor A. McKusick - updated : 7/13/2000<br>Victor A. McKusick - updated : 9/15/1998<br>Victor A. McKusick - updated : 8/3/1998
|
|
</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 : 1/25/1991
|
|
</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">
|
|
carol : 10/04/2023
|
|
</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">
|
|
carol : 03/08/2022<br>carol : 01/29/2018<br>carol : 01/26/2018<br>carol : 11/22/2017<br>carol : 06/24/2016<br>alopez : 7/9/2015<br>alopez : 4/2/2013<br>terry : 4/1/2013<br>carol : 11/9/2012<br>carol : 6/6/2012<br>terry : 5/17/2012<br>carol : 11/4/2011<br>terry : 8/19/2011<br>carol : 6/20/2011<br>carol : 6/17/2011<br>wwang : 2/28/2011<br>terry : 2/24/2011<br>wwang : 2/1/2010<br>ckniffin : 1/25/2010<br>terry : 6/3/2009<br>wwang : 4/29/2009<br>ckniffin : 4/13/2009<br>wwang : 11/12/2008<br>terry : 11/6/2008<br>mgross : 2/1/2008<br>mgross : 1/23/2008<br>alopez : 2/2/2007<br>terry : 1/31/2007<br>wwang : 8/22/2006<br>ckniffin : 8/11/2006<br>mgross : 3/17/2005<br>mgross : 3/17/2005<br>mgross : 3/17/2005<br>tkritzer : 2/7/2005<br>terry : 1/31/2005<br>tkritzer : 9/7/2004<br>terry : 8/24/2004<br>terry : 6/28/2004<br>terry : 2/2/2004<br>terry : 2/2/2004<br>tkritzer : 1/22/2004<br>terry : 1/21/2004<br>cwells : 12/24/2003<br>terry : 12/23/2003<br>tkritzer : 4/16/2003<br>terry : 4/10/2003<br>cwells : 3/28/2002<br>terry : 3/22/2002<br>alopez : 1/30/2001<br>mcapotos : 8/8/2000<br>alopez : 7/21/2000<br>terry : 7/13/2000<br>alopez : 12/27/1999<br>mgross : 12/2/1999<br>carol : 10/27/1999<br>terry : 10/26/1999<br>carol : 9/18/1998<br>terry : 9/15/1998<br>carol : 8/4/1998<br>terry : 8/3/1998<br>mark : 6/7/1996<br>mark : 3/29/1995<br>mimadm : 11/5/1994<br>davew : 7/13/1994<br>carol : 5/27/1994<br>warfield : 4/21/1994<br>carol : 11/12/1993
|
|
</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> 151623
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
|
|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
LI-FRAUMENI SYNDROME; LFS
|
|
|
|
</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">
|
|
SARCOMA FAMILY SYNDROME OF LI AND FRAUMENI<br />
|
|
SBLA SYNDROME
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
LI-FRAUMENI-LIKE SYNDROME, INCLUDED; LFL, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 428850001;
|
|
|
|
|
|
|
|
|
|
<strong>ORPHA:</strong> 524;
|
|
|
|
|
|
<strong>DO:</strong> 0111503;
|
|
|
|
|
|
</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">
|
|
17p13.1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Li-Fraumeni syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
151623
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
TP53
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
191170
|
|
</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 Li-Fraumeni syndrome (LFS) is caused by heterozygous mutation in the p53 gene (TP53; 191170) on chromosome 17p13.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous inherited cancer syndrome. LFS is characterized by autosomal dominant inheritance and early onset of tumors, multiple tumors within an individual, and multiple affected family members. In contrast to other inherited cancer syndromes, which are predominantly characterized by site-specific cancers, LFS presents with a variety of tumor types. The most common types are soft tissue sarcomas and osteosarcomas, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma. Classic LFS is defined as a proband with a sarcoma before the age of 45 years and a first-degree relative with any cancer before the age of 45 years and 1 additional first- or second-degree relative in the same lineage with any cancer before the age of 45 years or a sarcoma at any age (Li et al., 1988). Li-Fraumeni-like syndrome (LFL) is defined as a proband with any childhood cancer, or a sarcoma, brain tumor, or adrenocortical tumor before the age of 45 years, plus a first- or second-degree relative in the same lineage with a typical LFS tumor at any age, and an additional first- or second-degree relative in the same lineage with any cancer before the age of 60 years (Birch et al., 1994). A less restrictive definition of LFL is 2 different LFS-related tumors in first- or second-degree relatives at any age (Eeles, 1995). Approximately 70% of LFS cases and 40% of LFL cases contain germline mutations in the p53 gene on chromosome 17p13.1 (Bachinski et al., 2005). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In reviewing medical records and death certificates of 648 childhood rhabdomyosarcoma patients, Li and Fraumeni (1969) identified 4 families in which sibs or cousins had a childhood sarcoma. These 4 families also had striking histories of breast cancer and other neoplasms, suggesting a new familial cancer syndrome of diverse tumors. Subsequent prospective studies confirmed the high risk in family members of the tumor types that comprise LFS (Li and Fraumeni, 1982). Studies in other geographic and ethnic groups by Birch et al. (1984, 1990) corroborated the syndrome. The spectrum of cancers in the syndrome was shown to include, in addition to breast cancer and soft tissue sarcomas, brain tumors, osteosarcoma, leukemia, and adrenocortical carcinoma. </p><p>Fraumeni et al. (1975) described a kindred in which in 1 sibship of 9 adults, 4 died of lymphocytic or histiocytic lymphomas and 1, a male, of Waldenstrom macroglobulinemia complicated by adenocarcinoma of the lung. In the next generation, 1 person died of Hodgkin disease; 4 of 9 healthy persons had impaired lymphocyte transformation with phytohemagglutinin, and 3 of these had polyclonal elevation of IgM. Subsequent to the studies, adenocarcinoma of the lung developed in 1 of those with an immune defect, a woman, and her 3-year-old grandson developed lymphocytic leukemia. This was the first suggestion of a genetic or immunologic basis of lung adenocarcinoma. </p><p>Pearson et al. (1982) reported 2 families resembling that reported by Li and Fraumeni (1969). In 1, the mother had breast cancer and 3 of her 4 children had adrenocortical carcinoma, medulloblastoma, and rhabdomyosarcoma; in the other, the mother had breast cancer and 2 of her 3 children had adrenocortical carcinoma and rhabdomyosarcoma. </p><p>Mulvihill (1982) used the designation sarcoma family syndrome of Li and Fraumeni for the familial association of breast cancer, soft tissue sarcoma, and other tumors. Hartley et al. (1987) referred to this as the SBLA syndrome, a designation derived from the tumors that occur in this cancer family syndrome: sarcoma, breast and brain tumors, leukemia, laryngeal and lung cancer, and adrenal cortical carcinoma (Lynch et al., 1978). </p><p>Possible component tumors of LFS are melanoma, gonadal germ cell tumors, and carcinomas of the lung, pancreas, and prostate (Strong et al., 1987; Li et al., 1988). The diverse tumor types in family members characteristically develop at unusually early ages, and multiple primary tumors are frequent. By segregation analysis, Strong et al. (1987) demonstrated that the observed cancer distribution in families best fit a rare autosomal dominant gene model. The model also predicted that in families at risk the probability of developing any invasive cancer (excluding carcinomas of the skin) reaches almost 50% by age 30, when only 1% of the general population has developed cancer. More than 90% of the gene carriers would develop cancer by age 70 (review by Malkin et al., 1990). </p><p>Hisada et al. (1998) quantified the incidence of second and third primary cancers in individuals from 24 LFS families originally diagnosed with cancer between 1968 and 1986. Among 200 LFS family members diagnosed with cancer, 30 (15%) developed a second cancer. Eight individuals (4%) had a third cancer, while 4 (2%) eventually developed a fourth cancer. Overall, the relative risk of occurrence of a second cancer was 5.3, with a cumulated probability of second cancer occurrence of 57% at 30 years after diagnosis of a first cancer. Relative risks of second cancers occurring in families with this syndrome were 83.0, 9.7, and 1.5 for individuals with a first cancer at ages 0 to 19 years, 20 to 44 years, and 45 years or more, respectively. Thirty (71%) of 42 subsequent cancers in this group were component cancers of LFS. </p><p>Masciari et al. (2011) reviewed 62 TP53 mutation-positive families for gastric cancer. There were 429 cancer-affected individuals. In the 62 families gastric cancer was the diagnosis in the lineages of 21 (4.9%) subjects from 14 families (22.6%). The mean and median ages at gastric cancer diagnosis were 43 and 36 years, respectively (range: 24-74 years), significantly younger compared with the median age at diagnosis in the general population based on Surveillance Epidemiology and End Results data (71 years). Five (8.1%) families reported 2 or more cases of gastric cancer, and 6 (9.7%) families had cases of both colorectal and gastric cancers. No association was seen between phenotype and type/location of the TP53 mutations. Pathology review of the available tumors revealed both intestinal and diffuse histologies. Masciari et al. (2011) concluded that early-onset gastric cancer seems to be a component of Li-Fraumeni syndrome, suggesting the need for early and regular endoscopic screening in individuals with germline TP53 mutations, particularly among those with a family history of gastric cancer. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Li-Fraumeni syndrome shows autosomal dominant inheritance. The lifetime penetrance is high: by age 50, women have an overall higher risk (93%) of developing cancer compared to men (68%), as well as an earlier age at onset (29 years in women vs 40 years in men). Gonzalez et al. (2009) identified TP53 mutations in 75 of 341 patients with early-onset cancer sent for TP53 testing. Family history was available for all 341 patients. Five (7%) of 75 patients with TP53 mutations were confirmed to have de novo mutations, and 4 (80%) of the 5 patients with de novo mutations had multiple primary cancers. Ten of 75 patients with TP53 mutations likely had de novo germline mutations by family history. Gonzalez et al. (2009) estimated that the frequency of de novo TP53 mutations resulting in Li-Fraumeni syndrome may be as high as 20% (15 of 75). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Clinical Management</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Villani et al. (2016) introduced a clinical surveillance program (The Toronto Protocol) using physical examination and frequent biochemical and imaging studies (consisting of whole body MRI, brain MRI, breast MRI, mammography, abdominal and pelvic ultrasound, and colonoscopy) at 3 tertiary care centers in Canada and the USA on January 1, 2004, for carriers of TP53 pathogenic variants. After confirmation of TP53 mutation, participants either chose to undergo surveillance or chose not to undergo surveillance. Patients could cross over between groups at any time. The primary outcome measure was detection of symptomatic tumors by surveillance investigations. The secondary outcome measure was 5-year overall survival established from a tumor diagnosed symptomatically (in the nonsurveillance group) versus one diagnosed by surveillance. Villani et al. (2016) completed survival analyses using an as-treated approach. Between January 1, 2004 and July 1, 2015, Villani et al. (2016) identified 89 carriers of TP53 pathogenic mutations in 39 unrelated families, of whom 40 (45%) agreed to surveillance and 49 (55%) declined surveillance. Nineteen patients (21%) crossed over from nonsurveillance to the surveillance group, giving a total of 59 individuals (66%) undergoing surveillance for a median of 32 months (IQR 12-87). Forty asymptomatic tumors have been detected in 19 (32%) of 59 patients who underwent surveillance. Two additional cancers were diagnosed between surveillance assessments (false negatives) and 2 biopsied lesions were nonneoplastic entities on pathologic review (false positives). Among the 49 individuals who initially declined surveillance, 61 symptomatic tumors were diagnosed in 43 patients (88%). Twenty-one (49%) of the 43 individuals not on surveillance who developed cancer were alive compared with 16 (84%) of the 19 individuals undergoing surveillance who developed cancer (p = 0.012) after a median follow-up of 46 months for those not on surveillance and 38 months for those on surveillance. Five-year overall survival was 88.8% (95% CI 78.7-100) in the surveillance group and 59.6% (47.2-75.2) in the nonsurveillance group (p = 0.0132). Based on these findings, Villani et al. (2016) concluded that long-term compliance with a comprehensive surveillance protocol for early tumor detection in individuals with pathogenic TP53 variants is feasible and that early tumor detection through surveillance is associated with improved long-term survival. The authors suggested incorporation of this approach into clinical management of these patients. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>LFS1 results from mutation in the TP53 gene, which maps to chromosome 17p13.1.</p><p>To data on a set of kindreds with Li-Fraumeni syndrome, Shete et al. (2002) applied a method they developed to incorporate individual-specific liability classes into linkage analysis. The approach yielded higher lod scores and more accurate estimates of the recombination fraction in the families showing linkage. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Because tumor suppressor genes had been found to be associated with familial neoplasms, Malkin et al. (1990) suspected mutation in this type of gene in LFS. The RB1 gene (614041) was an unlikely candidate for a germline mutation in LFS because retinoblastoma (180200) had not been observed in these families. On the other hand, the TP53 gene was a more likely candidate because inactivating mutations therein had been associated with sporadic osteosarcomas, soft tissue sarcomas, brain tumors, leukemias, and carcinomas of the lung and breast. Furthermore, transgenic mice carrying a mutant p53 gene have an increased incidence of osteosarcomas, soft tissue sarcomas, adenocarcinomas of the lung, and adrenal and lymphoid tumors--all tumors that occur as part of LFS. Such was the basis for the successful search for p53 mutations in this disorder (see 191170.0001). </p><p>To determine the frequency and distribution of germline p53 mutations in LFS families, Frebourg et al. (1995) sequenced the 10 coding exons of TP53 in lymphocytes and fibroblast cell lines derived from 15 families with the syndrome. Germline mutations were observed in 8 such families; of these, 6 were missense mutations located between exons 5 and 8. One mutation was a nonsense mutation in exon 6 and one was a splicing mutation in intron 4; each of these mutations generated aberrantly short p53 RNAs. The study indicated that most germline p53 mutations in LFS are located between exons 5 and 8 and that approximately 50% of patients with LFS have no germline mutations in the coding region of the p53 gene. Significantly, in 3 families, a mutation of the p53 gene was observed in a fibroblast cell line derived from the proband, but the mutation was not found in affected relatives in 2 families or in the blood from 1 of the probands. This indicated that the mutation probably occurred during cell culture; thus, it is necessary that analysis for germline p53 mutations be performed on cells that have not been grown in vitro. </p><p>Varley et al. (1997) stated that more than 50 families had been identified with LFS caused by germline TP53 mutations. LFS is defined by strict clinical criteria, described by Li et al. (1988). This definition has been relaxed to include Li-Fraumeni-like (LFL) cases (Birch et al., 1994). Varley et al. (1997) detected mutations in TP53 in approximately 70% of LFS and 20% of LFL families, when all exons, including noncoding regions, were sequenced. </p><p>Chompret et al. (2001) reported a family study of 2,691 children with a history of solid tumor before the age of 18. A subgroup of 239 children had in addition a family history of at least 1 cancer affecting a first- or second-degree relative before the age of 46 or multiple primary cancers in the proband. Among these 239, 211 had at least 1 first- or second-degree relative affected, 16 had at least 2 primary tumors, and 12 fulfilled both criteria. They performed genotyping of p53 and found mutations in 9 individuals from the first group, 1 in the second, and 5 in the third. Chompret et al. (2001) calculated sensitivity and predictive value of p53 mutation testing using various degrees of stringency of selection criteria and concluded that p53 mutation testing should be considered in families where there is (1) a proband affected by a narrow spectrum cancer (sarcoma, brain tumor, breast cancer, adrenocortical tumor) before 36 years, and at least 1 first- or second-degree relative affected by a narrow spectrum tumor (other than breast cancer if the proband is affected by breast cancer) before the age of 46, or by multiple primary tumors; (2) a proband with multiple primary tumors, 2 of which belong to the narrow spectrum and the first of which occurred before 36 years, whatever the family history; (3) a proband with adrenocortical carcinoma, whatever the age of onset or family history. Using such criteria, they expected to find a mutation in 20% of cases and to miss 20% of mutations that would be detected by the least stringent criteria. </p><p>Hwang et al. (2003) stated that germline mutations in the p53 gene had been identified in 50 to 70% of families with LFS. To characterize cancer risk in heterozygous p53 mutation carriers, they analyzed cancer incidence in 56 germline p53 mutation carriers and 3,201 noncarriers from 107 kindreds ascertained through patients with childhood soft tissue sarcoma. Members of these kindreds were systematically followed for more than 20 years for cancer incidence and their p53 gene status was evaluated. Hwang et al. (2003) identified 7 kindreds with germline p53 mutations that included missense and truncation mutation types. A significantly higher cancer risk was found in female carriers than in male carriers, a difference not explained by an excess of sex-specific cancer. The calculated standardized incidence ratio (SIR) showed that mutation carriers had a risk for all types of cancer that was much higher than that for the general population, whereas noncarriers had a risk for all types of cancer that was similar to that in the general population. The calculated SIRs showed a higher risk by more than 100-fold for sarcoma, female breast cancer, and hematologic malignancy for the p53 mutation carriers and agreed with the findings of an earlier segregation analysis based on the same cohort (Kleihues et al., 1997). </p><p>Varley (2003) reviewed the findings of Birch et al. (2001), who studied the distribution of cancers in carriers of germline TP53 mutations from 28 families in which all cancers were verified and the ages of all family members, affected and unaffected, were known. They found a highly significant difference from the expected cancer distribution in the general population. The tumors originally identified as being components of Li-Fraumeni syndrome were found to be strongly associated with a germline TP53 mutation, with the exception of leukemia, which was not found to be a major component. However, Wilms tumor and malignant phyllode tumors of the breast were found at significantly higher frequency. (Phyllode is a term applied to tumors that on section show a lobulated, leaf-like appearance.) The increased cancer risk was most marked at younger ages and decreased with age. The only common adult epithelial tumor apart from breast that could be found at an increased frequency was pancreas, with no increased risk of lung, ovary, bladder, bowel, or head and neck tumors. The latter observation was particularly interesting because somatic TP53 mutations are found in approximately 60% of sporadic tumors at these sites (Soussi et al., 2000). The tissue-cell specificity associated with inheritance of a germline TP53 mutation is very striking. </p><p>Bendig et al. (2004) sought to identify germline mutations in the TP53 gene in 5 index cases of German and Swiss origin with cancers typical of Li-Fraumeni syndrome. They identified 5 mutations, of which 3 were found in families with a strong history of LFS in several generations and 2 seemingly arose de novo. Bendig et al. (2004) concluded that the frequent identification of de novo germline mutations emphasizes the importance of mutation analyses of the TP53 gene in young patients with malignancies typical for LFS but without a positive family history of this tumor syndrome. </p><p>Wang et al. (2013) reported on members of families with Li-Fraumeni syndrome who carried germline mutations in the TP53 gene. As compared with family members who are not carriers and with healthy volunteers, family members with these mutations have increased oxidative phosphorylation of skeletal muscle. Basic experimental studies of tissue samples from patients with the Li-Fraumeni syndrome and a mouse model of the syndrome supported this in vivo finding of increased mitochondrial function. Wang et al. (2013) concluded that their results suggested that p53 regulates bioenergetic homeostasis in humans. </p><p><strong><em>Other Genetic Abnormalities</em></strong></p><p>
|
|
Shlien et al. (2008) found that patients with TP53 mutations had significantly higher numbers of germline copy number variation (CNV) compared to controls. A microarray analysis counting CNVs on autosomal chromosomes comprising of 2 or more SNP probes identified 3,884 CNVs in genomic DNA from 770 healthy individuals. The median number of CNVs detected per control individual was 3, with 75% of the population having 4 or fewer CNVs. In individuals from 11 LFS families with TP53 mutations, the CNV mean was 12.19 per person, with 75% having 10 or fewer CNVs. The difference from controls was statistically significant (p = 0.01). The majority of specific CNVs observed in LFS families were acquired and not found in either parent. There was also a correlation between increased CNV number and cancer development among the LFS families, and analysis of tumor samples showed somatic increases in CNV. Shlien et al. (2008) suggested that CNVs represent regions of genomic instability and early neoplastic transformation. </p><p>Shlien et al. (2010) screened 4,524 patients with diverse clinical phenotypes for DNA dosage changes via array CGH or MLPA and identified 8 probands with a microdeletion on chromosome 17p13.1, at the TP53 (191170) locus. In 4 of the patients, who had childhood cancer and pedigrees consistent with Li-Fraumeni syndrome, deletions limited to the TP53 gene were found which deleted between 1 and 10 of the 11 exons. Another 4 patients, with a noncancer neurocognitive phenotype (613776), had larger deletions at 17p13.1, encompassing the entire TP53 gene and 26 to 85 other fully deleted genes. Shlien et al. (2010) demonstrated that mRNA expression levels of TP53 and TP53-dependent genes were altered in patients with partial, but not complete, deletions, which was consistent with mutant TP53-initiated tumorigenesis in the former group but not in the latter. The authors stated that their data supported a model in which partial deletions lead to the expression of a truncated protein, rather than the complete absence of it due to nonsense-mediated decay. Truncated and wildtype protein would oligomerize to form a defective TP53 tetramer, leading to a dominant-negative or gain-of-function effect similar to that observed with certain missense mutations, resulting in inhibition of wildtype TP53 function. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Olivier et al. (2003) described a database for collecting information on families carrying a germline mutation in the TP53 gene and on families affected with Li-Fraumeni syndromes, both Li-Fraumeni and Li-Fraumeni-like syndromes. Data from the published literature was included. They described analysis of 265 families/individuals with LFS/LFL. In classic LFS families with a germline TP53 mutation (83 families), the mean age of onset of breast cancer was significantly lower than in LFS families (16 families) without a TP53 mutation (34.6 vs. 42.5 years; P = 0.0035). In individuals with a TP53 mutation, a correlation between the genotype and phenotype was found: brain tumors were associated with missense TP53 mutations located in the DNA-binding loop that contact the minor groove of DNA (P = 0.01), whereas adrenal gland carcinomas were associated with missense mutations located in the loops opposing the protein-DNA contact surface (P = 0.003). Finally, mutations likely to result in a null phenotype (absence of the protein or loss of function) were associated with earlier onset brain tumors (P = 0.004). These observations were considered to have clinical implications for genetic testing and tumor surveillance in LFS/LFL families. </p><p>Capponcelli et al. (2005) identified a mutation in the TP53 gene (Y220S; 191170.0039) in a mother and her 3 children with Li-Fraumeni syndrome. All affected family members had a very aggressive clinical phenotype associated with resistance to doxorubicin and early death from cancer. In vitro studies showed that the mutation conferred increased cellular resistance to doxorubicin treatment, perhaps by inducing expression of peroxiredoxin II (PRDX2; 600538) and thioredoxin (TXN; 187700), both of which reduce reactive oxygen species. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Other Features</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Choriocarcinoma</em></strong></p><p>
|
|
Patrier-Sallebert et al. (2015) reported a gestational choriocarcinoma (CC) that developed in a female partner of a male patient with LFS; the CC carried a germline TP53 (191170) mutation initially detected in this LFS patient. The authors then identified 78 fathers who were carriers of a germline TP53 mutation. Among the 213 corresponding pregnancies, Patrier-Sallebert et al. (2015) found 2 other cases of gestational CC in the female partners, and estimated that gestational CC occurs in approximately 1% of the deliveries in female partners of TP53 mutation carriers. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Heterogeneity</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Mutations in p53 had not been detected in approximately 30% of LFS families. To address the possibility either that TP53 mutations were missed or that another predisposing gene is altered in LFS, Evans et al. (1998) used a variety of methods to determine the TP53 status in a large LFS kindred. A transcriptional activation assay on exons 4 to 10 of TP53 excluded a mutation within the DNA-binding domain. SSCP analysis, using intronic primers and sequencing of all the coding exons and intron/exon junctions, also yielded no mutations. Finally, linkage analysis excluded potential mutations in the noncoding regions of TP53. The family had been ascertained through systematic surveys of cancer in relatives of 382 childhood osteosarcoma patients. Classic LFS was defined as the diagnosis of a sarcoma in an individual before 45 years of age, having 2 first-degree relatives with cancer before the age of 45 years. In the LFS kindred studied, in addition to osteosarcoma in the proband, a sister had osteosarcoma and the mother had breast cancer before the age of 45 years. There was also lung cancer in the family as well as cancers of the ovary, thyroid, tongue, and kidney. Thirteen members were affected in 7 sibships in 3 generations. </p><p>Lynch et al. (2000) reported extensive follow-up of the family described by Lynch et al. (1978); a remarkable excess of brain tumors became evident in the update. One patient in the direct genetic lineage had a rhabdomyosarcoma of the eyelid at age 29 months and, at age 14 years, was diagnosed with lymphoblastic lymphoma/acute lymphoblastic leukemia. This same patient also had Sturge-Weber syndrome (185300), which seemingly had not previously been identified in Li-Fraumeni syndrome. No p53 germline mutation was identified in any affected members of this family. </p><p>In affected members of a large pedigree with tumors suggestive of a Li-Fraumeni-like syndrome, in which mutation in the TP53 gene had been excluded, Evans et al. (2008) identified a deletion of exons 14 to 16 in the BRCA2 gene by multiplex ligation-dependent probe amplification (MLPA) assay. Noting that other BRCA2 families have been reported with LFS spectrum sarcomas, the authors concluded that BRCA2 clearly accounts for a proportion of LFS/LFL families negative for TP53 mutations, but that it is likely that TP53 is the only LF-specific gene and that TP53-negative families are due to mutations in a variety of other, mostly known, genes. </p><p><strong><em>Exclusion Studies</em></strong></p><p>
|
|
In a Turkish family with Li-Fraumeni syndrome, Guran et al. (1999) demonstrated that the propositus with seminoma and his daughter with medulloblastoma had a hereditary TP53 mutation, lys292 to ile (K292I; 191170.0034), but also in analyses of tumor tissues had an ala94-to-glu missense mutation of the CDKN2A gene. Full blood analysis in the 2 cases revealed no CDKN2A mutation. This was the first time that a mutation in CDKN2A had been observed in Li-Fraumeni syndrome. Burt et al. (1999) excluded CDKN2A (600160) on chromosome 9 and PTEN (601728) on chromosome 10 as the cause of either LFS or LFL. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>The heterogeneity in the tumor spectrum and latency in patients with LFS due to inherited mutations in p53 suggest risk modifiers at loci other than the major gene. Evans et al. (2004) developed a mouse model to investigate these risk modifiers. Inbred CE/J mice, which succumbed to multiple types of tumors similar to those found in LFS, were crossed with the p53 null mouse. In this cross, the authors found evidence for a genetic modifier of p53, Mop1, based on an unexpected mix of genotypes in the F2 progeny. A model in which a recessive CE/J allele in combination with p53 heterozygosity or homozygosity results in lethality most closely fitted the data. Using simple sequence length polymorphism analysis of the entire genome, Evans et al. (2004) identified a putative chromosomal region for this modifier of p53 on mouse chromosome 11 centromeric to p53. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>History</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Bachinski et al. (2005) studied a series of LFS kindreds with no p53 or CHEK2 (604373) mutations. Using a genomewide scan for linkage with complementing parametric and nonparametric analysis methods, they mapped a novel locus, previously designated Li-Fraumeni syndrome-3 (LFS3), to a 4-cM region on chromosome 1q23. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Li and Fraumeni (1969); Li and Fraumeni (1975); Lynch et al. (1985)
|
|
</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">
|
|
Bachinski, L. L., Olufemi, S.-E., Zhou, X., Wu, C.-C., Yip, L., Shete, S., Lozano, G., Amos, C. I., Strong, L. C., Krahe, R.
|
|
<strong>Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23.</strong>
|
|
Cancer Res. 65: 427-431, 2005.
|
|
|
|
|
|
[PubMed: 15695383]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bendig, I., Mohr, N., Kramer, F., Weber, B. H. F.
|
|
<strong>Identification of novel TP53 mutations in familial and sporadic cancer cases of German and Swiss origin.</strong>
|
|
Cancer Genet. Cytogenet. 154: 22-26, 2004.
|
|
|
|
|
|
[PubMed: 15381368]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.cancergencyto.2004.02.017]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Birch, J. M., Alston, R. D., McNally, R. J. Q., Evans, D. G. R., Kelsey, A. M., Harris, M., Eden, O. B., Varley, J. M.
|
|
<strong>Relative frequency and morphology of cancers in carriers of germline TP53 mutations.</strong>
|
|
Oncogene 20: 4621-4628, 2001.
|
|
|
|
|
|
[PubMed: 11498785]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.onc.1204621]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Birch, J. M., Hartley, A. L., Blair, V., Kelsey, A. M., Harris, M., Teare, M. D., Jones, P. H. M.
|
|
<strong>Identification of factors associated with high breast cancer risk in the mothers of children with soft tissue sarcoma.</strong>
|
|
J. Clin. Oncol. 8: 583-590, 1990.
|
|
|
|
|
|
[PubMed: 2313328]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1200/JCO.1990.8.4.583]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Birch, J. M., Hartley, A. L., Marsden, H. B., Harris, M., Swindell, R.
|
|
<strong>Excess risk of breast cancer in the mothers of children with soft tissue sarcomas.</strong>
|
|
Brit. J. Cancer 49: 325-331, 1984.
|
|
|
|
|
|
[PubMed: 6704308]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/bjc.1984.51]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Birch, J. M., Hartley, A. L., Tricker, K. J., Prosser, J., Condie, A., Kelsey, A. M., Harris, M., Jones, P. H. M., Binchy, A., Crowther, D., Craft, A. W., Eden, O. B., Evans, D. G. R., Thompson, E., Mann, J. R., Martin, J., Mitchell, E. L. D., Santibanez-Koref, M. F.
|
|
<strong>Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.</strong>
|
|
Cancer Res. 54: 1298-1304, 1994.
|
|
|
|
|
|
[PubMed: 8118819]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Burt, E. C., McGown, G., Thorncroft, M., James, L. A., Birch, J. M., Varley, J. M.
|
|
<strong>Exclusion of the genes CDKN2 and PTEN as causative gene defects in Li-Fraumeni syndrome.</strong>
|
|
Brit. J. Cancer 80: 9-10, 1999.
|
|
|
|
|
|
[PubMed: 10389970]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.bjc.6690313]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Capponcelli, S., Pedrini, E., Cerone, M. A., Corti, V., Fontanesi, S., Alessio, M., Bachi, A., Soddu, S., Ribatti, D., Picci, P., Helman, L. J., Cantelli-Forti, G., Sangiorgi, L.
|
|
<strong>Evaluation of the molecular mechanisms involved in the gain of function of a Li-Fraumeni TP53 mutation.</strong>
|
|
Hum. Mutat. 26: 94-103, 2005.
|
|
|
|
|
|
[PubMed: 15977174]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.20192]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chompret, A., Abel, A., Stoppa-Lyonnet, D., Brugieres, L., Pages, S., Feunteun, J., Bonaiti-Pellie, C.
|
|
<strong>Sensitivity and predictive value of criteria for p53 germline mutation screening.</strong>
|
|
J. Med. Genet. 38: 43-47, 2001.
|
|
|
|
|
|
[PubMed: 11332399]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.38.1.43]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Eeles, R. A.
|
|
<strong>Germline mutations in the TP53 gene.</strong>
|
|
Cancer Surv. 25: 101-124, 1995.
|
|
|
|
|
|
[PubMed: 8718514]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Evans, D. G., Wu, C. L., Birch, J. M.
|
|
<strong>BRCA2: a cause of Li-Fraumeni-like syndrome. (Letter)</strong>
|
|
J. Med. Genet. 45: 62-63, 2008.
|
|
|
|
|
|
[PubMed: 18178637]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2007.054494]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Evans, S. C., Liang, M., Amos, C., Gu, X., Lozano, G.
|
|
<strong>A novel genetic modifier of p53, mop1, results in embryonic lethality.</strong>
|
|
Mammalian Genome 15: 415-423, 2004.
|
|
|
|
|
|
[PubMed: 15181534]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00335-004-2327-y]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Evans, S. C., Mims, B., McMasters, K. M., Foster, C. J., deAndrade, M., Amos, C. I., Strong, L. C., Lozano, G.
|
|
<strong>Exclusion of a p53 germline mutation in a classic Li-Fraumeni syndrome family.</strong>
|
|
Hum. Genet. 102: 681-686, 1998.
|
|
|
|
|
|
[PubMed: 9703430]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050761]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fraumeni, J. F., Jr., Wertelecki, W., Blattner, W. A., Jensen, R. D., Leventhal, B. G.
|
|
<strong>Varied manifestations of a familial lymphoproliferative disorder.</strong>
|
|
Am. J. Med. 59: 145-151, 1975.
|
|
|
|
|
|
[PubMed: 806230]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0002-9343(75)90333-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Frebourg, T., Barbier, N., Yan, Y., Garber, J. E., Dreyfus, M., Fraumeni, J., Jr., Li, F. P., Friend, S. H.
|
|
<strong>Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome.</strong>
|
|
Am. J. Hum. Genet. 56: 608-615, 1995.
|
|
|
|
|
|
[PubMed: 7887414]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gonzalez, K. D., Buzin, C. H., Noltner, K. A., Gu, D., Li, W., Malkin, D., Sommer, S. S.
|
|
<strong>High frequency of de novo mutations in Li-Fraumeni syndrome.</strong>
|
|
J. Med. Genet. 46: 689-693, 2009.
|
|
|
|
|
|
[PubMed: 19556618]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2008.058958]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guran, S., Tunca, Y., Imirzalioglu, N.
|
|
<strong>Hereditary TP53 codon 292 and somatic P16(INK4A) codon 94 mutations in a Li-Fraumeni syndrome family.</strong>
|
|
Cancer Genet. Cytogenet. 113: 145-151, 1999.
|
|
|
|
|
|
[PubMed: 10484981]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0165-4608(98)00276-3]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hartley, A. L., Birch, J. M., Marsden, H. B., Harris, M.
|
|
<strong>Malignant melanoma in families of children with osteosarcoma, chondrosarcoma, and adrenal cortical carcinoma.</strong>
|
|
J. Med. Genet. 24: 664-668, 1987.
|
|
|
|
|
|
[PubMed: 3480957]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.24.11.664]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hisada, M., Garber, J. E., Fung, C. Y., Fraumeni, J. F., Jr., Li, F. P.
|
|
<strong>Multiple primary cancers in families with Li-Fraumeni syndrome.</strong>
|
|
J. Nat. Cancer Inst. 90: 606-611, 1998.
|
|
|
|
|
|
[PubMed: 9554443]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/jnci/90.8.606]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hwang, S.-J., Lozano, G., Amos, C. I., Strong, L. C.
|
|
<strong>Germline p53 mutations in a cohort with childhood sarcoma: sex differences in cancer risk.</strong>
|
|
Am. J. Hum. Genet. 72: 975-983, 2003.
|
|
|
|
|
|
[PubMed: 12610779]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/374567]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kleihues, P., Schauble, B., zur Hausen, A., Esteve, J., Ohgaki, H.
|
|
<strong>Tumors associated with p53 germline mutations: a synopsis of 91 families.</strong>
|
|
Am. J. Path. 150: 1-13, 1997.
|
|
|
|
|
|
[PubMed: 9006316]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, F. P., Fraumeni, J. F., Jr.
|
|
<strong>Soft-tissue sarcomas, breast cancer, and other neoplasms: a familial syndrome?</strong>
|
|
Ann. Intern. Med. 71: 747-752, 1969.
|
|
|
|
|
|
[PubMed: 5360287]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-71-4-747]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, F. P., Fraumeni, J. F., Jr.
|
|
<strong>Familial breast cancer, soft-tissue sarcomas, and other neoplasms. (Letter)</strong>
|
|
Ann. Intern. Med. 83: 833-834, 1975.
|
|
|
|
|
|
[PubMed: 1200533]
|
|
|
|
|
|
[Full Text: https://doi.org/10.7326/0003-4819-83-6-833_2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, F. P., Fraumeni, J. F., Jr.
|
|
<strong>Prospective study of a family cancer syndrome.</strong>
|
|
JAMA 247: 2692-2694, 1982.
|
|
|
|
|
|
[PubMed: 7077763]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, F. P., Fraumeni, J. F.
|
|
<strong>Rhabdomyosarcoma in children: an epidemiologic study and identification of a familial cancer syndrome.</strong>
|
|
J. Nat. Cancer Inst. 43: 1365-1373, 1969.
|
|
|
|
|
|
[PubMed: 5396222]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Li, F. P., Fraumeni, J. R., Jr., Mulvihill, J. J., Blattner, W. A., Dreyfus, M. G., Tucker, M. A., Miller, R. W.
|
|
<strong>A cancer family syndrome in twenty-four kindreds.</strong>
|
|
Cancer Res. 48: 5358-5362, 1988.
|
|
|
|
|
|
[PubMed: 3409256]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lynch, H. T., Katz, D. A., Bogard, P. J., Lynch, J. F.
|
|
<strong>The sarcoma, breast cancer, lung cancer, and adrenocortical carcinoma syndrome revisited.</strong>
|
|
Am. J. Dis. Child. 139: 134-136, 1985.
|
|
|
|
|
|
[PubMed: 3976585]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1001/archpedi.1985.02140040032020]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lynch, H. T., McComb, R. D., Osborn, N. K., Wolpert, P. A., Lynch, J. F., Wszolek, Z. K., Sidransky, D., Steg, R. E.
|
|
<strong>Predominance of brain tumors in an extended Li-Fraumeni (SBLA) kindred, including a case of Sturge-Weber syndrome.</strong>
|
|
Cancer 88: 433-439, 2000.
|
|
|
|
|
|
[PubMed: 10640978]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(sici)1097-0142(20000115)88:2<433::aid-cncr26>3.0.co;2-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lynch, H. T., Mulcahy, G. M., Harris, R. E., Guirgis, H. A., Lynch, J. F.
|
|
<strong>Genetic and pathologic findings in a kindred with hereditary sarcoma breast cancer, brain tumors, leukemia, lung, laryngeal, and adrenal cortical carcinoma.</strong>
|
|
Cancer 41: 2055-2064, 1978.
|
|
|
|
|
|
[PubMed: 647640]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1097-0142(197805)41:5<2055::aid-cncr2820410554>3.0.co;2-x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Malkin, D., Li, F. P., Strong, L. C., Fraumeni, J. F., Jr., Nelson, C. E., Kim, D. H., Kassel, J., Gryka, M. A., Bischoff, F. Z., Tainsky, M. A., Friend, S. H.
|
|
<strong>Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms.</strong>
|
|
Science 250: 1233-1238, 1990. Note: Erratum: Science 259: 878 only, 1993.
|
|
|
|
|
|
[PubMed: 1978757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1978757]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Masciari, S., Dewanwala, A., Stoffel, E. M., Lauwers, G. Y., Zheng, H., Achatz, M. I., Riegert-Johnson, D., Foretova, L., Silva, E. M., Digianni, L., Verselis, S. J., Schneider, K., Li, F. P., Fraumeni, J., Garber, J. E., Syngal, S.
|
|
<strong>Gastric cancer in individuals with Li-Fraumeni syndrome.</strong>
|
|
Genet. Med. 13: 651-657, 2011.
|
|
|
|
|
|
[PubMed: 21552135]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1097/GIM.0b013e31821628b6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mulvihill, J. J.
|
|
<strong>Personal Communication.</strong>
|
|
Bethesda, Md. 6/11/1982.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Olivier, M. Goldgar, D. E., Sodha, N., Ohgaki, H., Kleihues, P., Hainaut, P., Eeles, R. A.
|
|
<strong>Li-Fraumeni and related syndromes: correlation between tumor type, family structure, and TP53 genotype.</strong>
|
|
Cancer Res. 63: 6643-6650, 2003.
|
|
|
|
|
|
[PubMed: 14583457]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Patrier-Sallebert, S., Bougeard, G., Baert-Desurmont, S., Lamy, A., Flaman, J.-M., Mansuy, L., Bronner, M., Lasset, C., Brugieres, L., Golfier, F., Frebourg, T.
|
|
<strong>Transmission of germline TP53 mutations from male carriers to female partners.</strong>
|
|
J. Med. Genet. 52: 145-146, 2015.
|
|
|
|
|
|
[PubMed: 25612911]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmedgenet-2014-102853]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pearson, A. D. J., Craft, A. W., Ratcliffe, J. M., Birch, J. M., Morris-Jones, P., Roberts, D. F.
|
|
<strong>Two families with the Li-Fraumeni cancer family syndrome.</strong>
|
|
J. Med. Genet. 19: 362-365, 1982.
|
|
|
|
|
|
[PubMed: 6958872]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.19.5.362]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shete, S., Amos, C. I., Hwang, S.-J., Strong, L. C.
|
|
<strong>Individual-specific liability groups in genetic linkage, with applications to kindreds with Li-Fraumeni syndrome.</strong>
|
|
Am. J. Hum. Genet. 70: 813-817, 2002.
|
|
|
|
|
|
[PubMed: 11822026]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/339370]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shlien, A., Baskin, B., Achatz, M. I. W., Stavropoulos, D. J., Nichols, K. E., Hudgins, L., Morel, C. F., Adam, M. P., Zhukova, N., Rotin, L., Novokmet, A., Druker, H., Shago, M., Ray, P. N., Hainaut, P., Malkin, D.
|
|
<strong>A common molecular mechanism underlies two phenotypically distinct 17p13.1 microdeletion syndromes.</strong>
|
|
Am. J. Hum. Genet. 87: 631-642, 2010.
|
|
|
|
|
|
[PubMed: 21056402]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2010.10.007]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shlien, A., Tabori, U., Marshall, C. R., Pienkowska, M., Feuk, L., Novokmet, A., Nanda, S., Druker, H., Scherer, S. W., Malkin, D.
|
|
<strong>Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 105: 11264-11269, 2008.
|
|
|
|
|
|
[PubMed: 18685109]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0802970105]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Soussi, T., Dehouche, K., Beroud, C.
|
|
<strong>p53 website and analysis of p53 gene mutations in human cancer: forging a link between epidemiology and carcinogenesis.</strong>
|
|
Hum. Mutat. 15: 105-113, 2000.
|
|
|
|
|
|
[PubMed: 10612830]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(200001)15:1<105::AID-HUMU19>3.0.CO;2-G]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Strong, L. C., Stine, M., Norsted, T. L.
|
|
<strong>Cancer in survivors of childhood soft tissue sarcoma and their relatives.</strong>
|
|
J. Nat. Cancer Inst. 79: 1213-1220, 1987.
|
|
|
|
|
|
[PubMed: 3480372]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Varley, J. M., Evans, D. G. R., Birch, J. M.
|
|
<strong>Li-Fraumeni syndrome: a molecular and clinical review.</strong>
|
|
Brit. J. Cancer 76: 1-14, 1997.
|
|
|
|
|
|
[PubMed: 9218725]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/bjc.1997.328]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Varley, J. M., McGown, G., Thorncroft, M., Santibanez-Koref, M. F., Kelsey, A. M., Tricker, K. J., Evans, D. G. R., Birch, J. M.
|
|
<strong>Germ-line mutations of TP53 in Li-Fraumeni families: an extended study of 39 families.</strong>
|
|
Cancer Res. 57: 3245-3252, 1997.
|
|
|
|
|
|
[PubMed: 9242456]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Varley, J. M.
|
|
<strong>Germline TP53 mutations and Li-Fraumeni syndrome.</strong>
|
|
Hum. Mutat. 21: 313-320, 2003. Erratum: Hum. Mutat. 21: 551 only, 2003.
|
|
|
|
|
|
[PubMed: 12619118]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10185]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Villani, A., Shore, A., Wasserman, J. D., Stephens, D., Kim, R. H., Druker, H., Gallinger, B., Naumer, A., Kohlmann, W., Novokmet, A., Tabori, U., Tijerin, M., Greer, M.-L. C., Finlay, J. L., Schiffman, J. D., Malkin, D.
|
|
<strong>Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: 11 year follow-up of a prospective observational study.</strong>
|
|
Lancet Oncol. 17: 1295-1305, 2016.
|
|
|
|
|
|
[PubMed: 27501770]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/S1470-2045(16)30249-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wang, P., Ma, W., Park, J.-Y., Celi, F. S., Arena, R., Choi, J. W., Ali, Q. A., Tripodi, D. J., Zhuang, J., Lago, C. U., Strong, L. C., Talagala, S. L., Balaban, R. S., Kang, J.-G., Hwang, P. M.
|
|
<strong>Increased oxidative metabolism in the Li-Fraumeni syndrome.</strong>
|
|
New Eng. J. Med. 368: 1027-1032, 2013.
|
|
|
|
|
|
[PubMed: 23484829]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMoa1214091]
|
|
|
|
|
|
</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 : 11/22/2017<br>Ada Hamosh - updated : 7/9/2015<br>Ada Hamosh - updated : 4/1/2013<br>Ada Hamosh - updated : 8/19/2011<br>Marla J. F. O'Neill - updated : 2/24/2011<br>Cassandra L. Kniffin - updated : 1/25/2010<br>Cassandra L. Kniffin - updated : 4/13/2009<br>Marla J. F. O'Neill - updated : 11/6/2008<br>Matthew B. Gross - updated : 2/1/2008<br>Victor A. McKusick - updated : 1/31/2007<br>Cassandra L. Kniffin - updated : 8/11/2006<br>Victor A. McKusick - updated : 3/17/2005<br>Victor A. McKusick - updated : 1/31/2005<br>Victor A. McKusick - updated : 8/24/2004<br>Victor A. McKusick - updated : 2/2/2004<br>Victor A. McKusick - updated : 1/21/2004<br>Victor A. McKusick - updated : 12/23/2003<br>Victor A. McKusick - updated : 4/10/2003<br>Victor A. McKusick - updated : 3/22/2002<br>Michael J. Wright - updated : 1/30/2001<br>Victor A. McKusick - updated : 7/13/2000<br>Victor A. McKusick - updated : 9/15/1998<br>Victor A. McKusick - updated : 8/3/1998
|
|
</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 : 1/25/1991
|
|
</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">
|
|
carol : 10/04/2023<br>carol : 03/08/2022<br>carol : 01/29/2018<br>carol : 01/26/2018<br>carol : 11/22/2017<br>carol : 06/24/2016<br>alopez : 7/9/2015<br>alopez : 4/2/2013<br>terry : 4/1/2013<br>carol : 11/9/2012<br>carol : 6/6/2012<br>terry : 5/17/2012<br>carol : 11/4/2011<br>terry : 8/19/2011<br>carol : 6/20/2011<br>carol : 6/17/2011<br>wwang : 2/28/2011<br>terry : 2/24/2011<br>wwang : 2/1/2010<br>ckniffin : 1/25/2010<br>terry : 6/3/2009<br>wwang : 4/29/2009<br>ckniffin : 4/13/2009<br>wwang : 11/12/2008<br>terry : 11/6/2008<br>mgross : 2/1/2008<br>mgross : 1/23/2008<br>alopez : 2/2/2007<br>terry : 1/31/2007<br>wwang : 8/22/2006<br>ckniffin : 8/11/2006<br>mgross : 3/17/2005<br>mgross : 3/17/2005<br>mgross : 3/17/2005<br>tkritzer : 2/7/2005<br>terry : 1/31/2005<br>tkritzer : 9/7/2004<br>terry : 8/24/2004<br>terry : 6/28/2004<br>terry : 2/2/2004<br>terry : 2/2/2004<br>tkritzer : 1/22/2004<br>terry : 1/21/2004<br>cwells : 12/24/2003<br>terry : 12/23/2003<br>tkritzer : 4/16/2003<br>terry : 4/10/2003<br>cwells : 3/28/2002<br>terry : 3/22/2002<br>alopez : 1/30/2001<br>mcapotos : 8/8/2000<br>alopez : 7/21/2000<br>terry : 7/13/2000<br>alopez : 12/27/1999<br>mgross : 12/2/1999<br>carol : 10/27/1999<br>terry : 10/26/1999<br>carol : 9/18/1998<br>terry : 9/15/1998<br>carol : 8/4/1998<br>terry : 8/3/1998<br>mark : 6/7/1996<br>mark : 3/29/1995<br>mimadm : 11/5/1994<br>davew : 7/13/1994<br>carol : 5/27/1994<br>warfield : 4/21/1994<br>carol : 11/12/1993
|
|
</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 5, 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>
|
|
|
|
|