Tumour evolution inferred by single-cell sequencing

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In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse `pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates.">  <meta property="og:type" content="article"> <meta property="og:title" content="Tumour evolution inferred by single-cell sequencing"> <meta property="og:site_name" content="NASA/ADS"> <meta property="og:description" content="Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse `pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates."> <meta property="og:url" content="https://ui.adsabs.harvard.edu/abs/2011Natur.472...90N/abstract"> <meta property="og:image" content="https://ui.adsabs.harvard.edu/styles/img/transparent_logo.svg"> <meta property="article:published_time" content="04/2011"> <meta property="article:author" content="Navin, Nicholas"> <meta property="article:author" content="Kendall, Jude"> <meta property="article:author" content="Troge, Jennifer"> <meta property="article:author" content="Andrews, Peter"> <meta property="article:author" content="Rodgers, Linda"> <meta property="article:author" content="McIndoo, Jeanne"> <meta property="article:author" content="Cook, Kerry"> <meta property="article:author" content="Stepansky, Asya"> <meta property="article:author" content="Levy, Dan"> <meta property="article:author" content="Esposito, Diane"> <meta property="article:author" content="Muthuswamy, Lakshmi"> <meta property="article:author" content="Krasnitz, Alex"> <meta property="article:author" content="McCombie, W. 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Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse `pseudodiploid' cells that do not travel to the metastatic site. 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<li class="author"><a href="/search/?q=author%3A%22Kendall%2C+Jude%22">Kendall, Jude</a> </li>; <li class="author"><a href="/search/?q=author%3A%22Troge%2C+Jennifer%22">Troge, Jennifer</a> </li>; <li class="author"><a href="/search/?q=author%3A%22Andrews%2C+Peter%22">Andrews, Peter</a> </li>; <li class="author"><a href="/search/?q=author%3A%22Rodgers%2C+Linda%22">Rodgers, Linda</a> </li>; <li class="author"><a href="/search/?q=author%3A%22McIndoo%2C+Jeanne%22">McIndoo, Jeanne</a> </li>; <li class="author"><a href="/search/?q=author%3A%22Cook%2C+Kerry%22">Cook, Kerry</a> </li>; <li class="author"><a href="/search/?q=author%3A%22Stepansky%2C+Asya%22">Stepansky, Asya</a> </li>; <li class="author"><a href="/search/?q=author%3A%22Levy%2C+Dan%22">Levy, Dan</a> </li>; <li class="author"><a href="/search/?q=author%3A%22Esposito%2C+Diane%22">Esposito, Diane</a> </li>; <li class="author"><a href="/search/?q=author%3A%22Muthuswamy%2C+Lakshmi%22">Muthuswamy, Lakshmi</a> </li>; <li class="author"><a href="/search/?q=author%3A%22Krasnitz%2C+Alex%22">Krasnitz, Alex</a> </li>; <li class="author"><a href="/search/?q=author%3A%22McCombie%2C+W.+Richard%22">McCombie, W. Richard</a> </li>; <li class="author"><a href="/search/?q=author%3A%22Hicks%2C+James%22">Hicks, James</a> </li>; <li class="author"><a href="/search/?q=author%3A%22Wigler%2C+Michael%22">Wigler, Michael</a> </li> </ul> </div> <div class="s-abstract-text"> <h4 class="sr-only">Abstract</h4> <p> Genomic analysis provides insights into the role of copy number variation in disease, but most methods are not designed to resolve mixed populations of cells. In tumours, where genetic heterogeneity is common, very important information may be lost that would be useful for reconstructing evolutionary history. Here we show that with flow-sorted nuclei, whole genome amplification and next generation sequencing we can accurately quantify genomic copy number within an individual nucleus. We apply single-nucleus sequencing to investigate tumour population structure and evolution in two human breast cancer cases. Analysis of 100 single cells from a polygenomic tumour revealed three distinct clonal subpopulations that probably represent sequential clonal expansions. Additional analysis of 100 single cells from a monogenomic primary tumour and its liver metastasis indicated that a single clonal expansion formed the primary tumour and seeded the metastasis. In both primary tumours, we also identified an unexpectedly abundant subpopulation of genetically diverse `pseudodiploid' cells that do not travel to the metastatic site. In contrast to gradual models of tumour progression, our data indicate that tumours grow by punctuated clonal expansions with few persistent intermediates. </p> </div> <br> <dl class="s-abstract-dl-horizontal"> <dt>Publication:</dt> <dd> <div id="article-publication">Nature</div> </dd> <dt>Pub Date:</dt> <dd>April 2011</dd> <dt>DOI:</dt> <dd> <span> <a href="/link_gateway/2011Natur.472...90N/doi:10.1038/nature09807" target="_blank" rel="noopener">10.1038/nature09807</a> <i class="fa fa-external-link"></i> </span> </dd> <dt>Bibcode:</dt> <dd> <a href="/abs/2011Natur.472...90N/abstract"> 2011Natur.472...90N </a> <i class="icon-help" title="The bibcode is assigned by the ADS as a unique identifier for the paper."></i> </dd> </dl> </article> </div> <div data-widget="ShowCitations"></div> <div data-widget="ShowReferences"></div> <div data-widget="ShowCoreads"></div> <div data-widget="ShowSimilar"></div> <div data-widget="ShowTableofcontents"></div> <div data-widget="ShowGraphics"></div> <div data-widget="ShowExportcitation" data-origin="abstract"></div> <div data-widget="ShowMetrics" data-allow-redirect="false"></div> <div data-widget="MetaTagsWidget"></div> </div> </div> </div> <div class="s-right-col-container col-xs-12 col-sm-12 col-md-3 col-lg-2 s-right-column" id="right-col-container" > <div data-widget="ShowResources"> <div data-reactroot="" class="s-right-col-widget-container" style="padding: 10px" > <div> <div class="resources__container"> <div class="resources__full__list"> <div class="resources__header__row"> <i class="fa fa-file-text-o" aria-hidden="true"> </i> <div class="resources__header__title">full text sources</div> </div> <div class="resources__content"> <div class="resources__content__title">Publisher</div> <div class="resources__content__links"> <span> <div class="resources__content__link__separator">|</div> </span> <span> <a href="/link_gateway/2011Natur.472...90N/PUB_HTML" rel="noopener" class="resources__content__link " > <i class="fa fa-file-text" aria-hidden="true"> </i> </a> </span> </div> </div> </div> </div> <div data-widget="ShowAssociated"> </div> </div> </div> </div> <div data-widget="ShowGraphicsSidebar"> </div> </div> </div> </div> </div> </div> </div> <div id="footer-container"> <div data-widget="FooterWidget"> <div class="footer s-footer"> <footer> <div class="__footer_wrapper"> <div class="__footer_brand"> 漏 The SAO/NASA Astrophysics Data System <div class="__footer_brand_extra"> <p> <i class="fa fa-envelope"></i> adshelp[at]cfa.harvard.edu </p> <p> The ADS is operated by the Smithsonian Astrophysical Observatory under NASA Cooperative Agreement <em>NNX16AC86A</em> </p> </div> <div class="__footer_brand_logos"> <a href="http://www.nasa.gov" target="_blank" rel="noopener"> <img src="/styles/img/nasa.svg" alt="NASA logo" id="nasa-logo"> </a> <a href="http://www.si.edu" target="_blank" rel="noopener"> <img id="smithsonian-logo" src="/styles/img/smithsonian.svg" alt="Smithsonian logo"> </a> <a href="https://www.cfa.harvard.edu/" target="_blank" rel="noopener"> <img src="/styles/img/cfa.png" title="Harvard Center for Astrophysics logo" id="cfa-logo"> </a> </div> </div> <div class="__footer_list"> <div class="__footer_list_title"> Resources </div> <ul class="__footer_links"> <li> <a href="/about/" target="_blank" rel="noopener"> <i class="fa fa-question-circle"></i> About ADS </a> </li> <li> <a href="//ui.adsabs.harvard.edu/help/" target="_blank" rel="noopener"> <i class="fa fa-info-circle"></i> ADS Help </a> </li> <li> <a href="//ui.adsabs.harvard.edu/help/whats_new/" target="_blank" rel="noopener"> <i class="fa fa-bullhorn"></i> What's New </a> </li> <li> <a href="/about/careers/" target="_blank" rel="noopener"> <i class="fa fa-group"></i> Careers@ADS </a> </li> </ul> </div> <div class="__footer_list"> <div class="__footer_list_title"> Social </div> <ul class="__footer_links"> <li> <a href="//twitter.com/adsabs" target="_blank" rel="noopener"> <i class="fa fa-twitter"></i> @adsabs </a> </li> <li> <a href="//ui.adsabs.harvard.edu/blog/" target="_blank" rel="noopener"> <i class="fa fa-newspaper-o"></i> ADS Blog </a> </li> </ul> </div> <div class="__footer_list"> <div class="__footer_list_title"> Project </div> <ul class="__footer_links"> <li> <a href="/core/never">Switch to full ADS</a> </li> <li> <a href="https://adsisdownorjustme.herokuapp.com/" target="_blank" rel="noopener">Is ADS down? 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// Add class "autocomplete-active": x[currentFocus].classList.add("autocomplete-active"); } function removeActive(x) { // Remove the "active" class from all autocomplete items: for (var i = 0; i < x.length; i++) { x[i].classList.remove("autocomplete-active"); } } function closeAllLists(elmnt) { // Close all autocomplete lists in the document, except the one passed as an argument: var x = document.getElementsByClassName("autocomplete-items"); for (var i = 0; i < x.length; i++) { if (elmnt != x[i] && elmnt != searchBox) { x[i].parentNode.removeChild(x[i]); } } } // Any other clicks in the document: document.addEventListener("click", function (e) { closeAllLists(e.target); }); } var autoList = [ { value: 'author:""', label: 'Author', match: 'author:"' }, { value: 'author:"^"', label: 'First Author', match: 'first author' }, { value: 'author:"^"', label: 'First Author', match: 'author:"^' }, { value: 'bibcode:""', label: 'Bibcode', desc: 'e.g. bibcode:1989ApJ...342L..71R', match: 'bibcode:"' }, { value: 'bibstem:""', label: 'Publication', desc: 'e.g. bibstem:ApJ', match: 'bibstem:"' }, { value: 'bibstem:""', label: 'Publication', desc: 'e.g. bibstem:ApJ', match: 'publication (bibstem)' }, { value: 'arXiv:', label: 'arXiv ID', match: 'arxiv:' }, { value: 'doi:', label: 'DOI', match: 'doi:' }, { value: 'full:""', label: 'Full text search', desc: 'title, abstract, and body', match: 'full:' }, { value: 'full:""', label: 'Full text search', desc: 'title, abstract, and body', match: 'fulltext' }, { value: 'full:""', label: 'Full text search', desc: 'title, abstract, and body', match: 'text' }, { value: 'year:', label: 'Year', match: 'year' }, { value: 'year:1999-2005', label: 'Year Range', desc: 'e.g. 1999-2005', match: 'year range' }, { value: 'aff:""', label: 'Affiliation', match: 'aff:' }, { value: 'abs:""', label: 'Search abstract + title + keywords', match: 'abs:' }, { value: 'database:astronomy', label: 'Limit to papers in the astronomy database', match: 'database:astronomy' }, { value: 'database:physics', label: 'Limit to papers in the physics database', match: 'database:physics' }, { value: 'title:""', label: 'Title', match: 'title:"' }, { value: 'orcid:', label: 'ORCiD identifier', match: 'orcid:' }, { value: 'object:', label: 'SIMBAD object (e.g. object:LMC)', match: 'object:' }, { value: 'property:refereed', label: 'Limit to refereed', desc: '(property:refereed)', match: 'refereed' }, { value: 'property:refereed', label: 'Limit to refereed', desc: '(property:refereed)', match: 'property:refereed' }, { value: 'property:notrefereed', label: 'Limit to non-refereed', desc: '(property:notrefereed)', match: 'property:notrefereed' }, { value: 'property:notrefereed', label: 'Limit to non-refereed', desc: '(property:notrefereed)', match: 'notrefereed' }, { value: 'property:eprint', label: 'Limit to eprints', desc: '(property:eprint)', match: 'eprint' }, { value: 'property:eprint', label: 'Limit to eprints', desc: '(property:eprint)', match: 'property:eprint' }, { value: 'property:openaccess', label: 'Limit to open access', desc: '(property:openaccess)', match: 'property:openaccess' }, { value: 'property:openaccess', label: 'Limit to open access', desc: '(property:openaccess)', match: 'openaccess' }, { value: 'doctype:software', label: 'Limit to software', desc: '(doctype:software)', match: 'software' }, { value: 'doctype:software', label: 'Limit to software', desc: '(doctype:software)', match: 'doctype:software' }, { value: 'property:inproceedings', label: 'Limit to papers in conference proceedings', desc: '(property:inproceedings)', match: 'proceedings' }, { value: 'property:inproceedings', label: 'Limit to papers in conference proceedings', desc: '(property:inproceedings)', match: 'property:inproceedings' }, { value: 'citations()', label: 'Citations', desc: 'Get papers citing your search result set', match: 'citations(' }, { value: 'references()', label: 'References', desc: 'Get papers referenced by your search result set', match: 'references(' }, { value: 'trending()', label: 'Trending', desc: 'Get papers most read by users who recently read your search result set', match: 'trending(' }, { value: 'reviews()', label: 'Review Articles', desc: 'Get most relevant papers that cite your search result set', match: 'reviews(' }, { value: 'useful()', label: 'Useful', desc: 'Get papers most frequently cited by your search result set', match: 'useful(' }, { value: 'similar()', label: 'Similar', desc: 'Get papers that have similar full text to your search result set', match: 'similar(' }, ]; // initiate the autocomplete function on the "q" element, and pass along the operators array as possible autocomplete values: inputBox = document.getElementById("q") if (inputBox) { inputBox.focus() // autofucs inputBox.setSelectionRange(inputBox.value.length, inputBox.value.length); // bring cursor to the end autocomplete(inputBox, autoList); } </script> <script> (function() { // turn off no-js if we have javascript document.documentElement.className = document.documentElement.className.replace("no-js", "js"); function getCookie(cname) { var name = cname + "="; var decodedCookie = decodeURIComponent(document.cookie); var ca = decodedCookie.split(';'); for (var i = 0; i < ca.length; i++) { var c = ca[i]; while (c.charAt(0) == ' ') { c = c.substring(1); } if (c.indexOf(name) == 0) { return c.substring(name.length, c.length); } } return ""; } (function() { // looks for the cookie, and sets true if its 'always' const coreCookie = getCookie('core') === 'always'; // only load bumblebee if we detect the core cookie and we are on abstract page if (coreCookie || (!(/^\/abs\//.test(document.location.pathname)) && !coreCookie)) { return; 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Tumour evolution inferred by single-cell sequencing - NASA/ADS