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<meta name="description" content="We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exh …"><meta name="keywords" content="pmid:27135926, PMC4910866, doi:10.1038/nature17676, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov&#x27;t, Research Support, U.S. Gov&#x27;t, Non-P.H.S., Serena Nik-Zainal, Helen Davies, Michael R Stratton, Breast Neoplasms / genetics*, Cohort Studies, DNA Mutational Analysis, DNA Replication / genetics, DNA, Neoplasm / genetics, Female, Genes, BRCA1, Genes, BRCA2, Genome, Human / genetics*, Genomics, Humans, Male, Mutagenesis, Mutation / genetics*, Mutation Rate, Oncogenes / genetics, Recombinational DNA Repair / genetics, PubMed Abstract, NIH, NLM, NCBI, National Institutes of Health, National Center for Biotechnology Information, National Library of Medicine, MEDLINE"><meta name="robots" content="index,nofollow,noarchive"><meta property="og:title" content="Landscape of somatic mutations in 560 breast cancer whole-genome sequences - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/27135926/"><meta property="og:description" content="We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exh …"><meta property="og:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:image:secure_url" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg"><meta property="og:type" content="website"><meta property="og:site_name" content="PubMed"><meta name="twitter:domain" content="pubmed.ncbi.nlm.nih.gov"><meta name="twitter:card" content="summary_large_image"><meta name="twitter:title" content="Landscape of somatic mutations in 560 breast cancer whole-genome sequences - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/27135926/"><meta name="twitter:description" content="We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exh …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 27135926 - PubMed</span>
<input type="hidden" name="email-subject" value="1 selected item: 27135926"/>
<input type="hidden" name="email-subject-hash" value="70fbe11b53ffb7b910499d7e8b7bf410fb27cce960526a95b235c574b7138edc"/>
</div>
<div class="action-panel-control-wrap">
<label for="email-to" class="action-panel-label required-field-asterisk">
To:
</label>
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
</div>
<div class="action-panel-control-wrap">
<label for="email-from" class="action-panel-label">
From:
</label>
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
</div>
<div class="action-panel-control-wrap">
<label for="email-citation-format" class="action-panel-label">
Format:
</label>
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
<option selected="selected" value="summary">Summary</option>
<option value="summary-text">Summary (text)</option>
<option value="abstract">Abstract</option>
<option value="abstract-text">Abstract (text)</option>
</select>
</div>
<div class="include-supplemental-container">
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="iUBsQBkzaRAiwxNPDcKomPftoloJa42ZzHlxtrNVKsnMqYTFgvnqQXL7Wp6V3FAj">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
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<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="iUBsQBkzaRAiwxNPDcKomPftoloJa42ZzHlxtrNVKsnMqYTFgvnqQXL7Wp6V3FAj">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
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<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="iUBsQBkzaRAiwxNPDcKomPftoloJa42ZzHlxtrNVKsnMqYTFgvnqQXL7Wp6V3FAj">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="27135926">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://doi.org/10.1038/nature17676"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3094&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=27135926&amp;db=pubmed&amp;nlmid=0410462"
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><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.nature.com-static-images-logos-nature-portfolio-120.png" alt="Nature Publishing Group full text link"><span class="text">
Nature Publishing Group
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/27135926/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=27135926&amp;db=pubmed&amp;nlmid=0410462"
title="Free full text at PubMed Central"
data-ga-category="full_text"
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Free PMC article
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<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/27135926/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/27135926/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="27135926" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F27135926%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="iUBsQBkzaRAiwxNPDcKomPftoloJa42ZzHlxtrNVKsnMqYTFgvnqQXL7Wp6V3FAj"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
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<h1 class="heading-title">
Landscape of somatic mutations in 560 breast cancer whole-genome sequences
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14
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15
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
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17
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18
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1
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data-ga-label="John A Foekens">John A Foekens</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam 3015CN, The Netherlands." href="#full-view-affiliation-7" ref="linksrc=author_aff">
7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
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20
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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21
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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22
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23
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24
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21
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25
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1
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1
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1
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1
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1
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26
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27
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data-ga-label="F Germán Rodríguez-González">F Germán Rodríguez-González</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam 3015CN, The Netherlands." href="#full-view-affiliation-7" ref="linksrc=author_aff">
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data-ga-label="Gilles Romieu">Gilles Romieu</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Oncologie Sénologie, ICM Institut Régional du Cancer, Montpellier, France." href="#full-view-affiliation-29" ref="linksrc=author_aff">
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data-ga-label="Anieta M Sieuwerts">Anieta M Sieuwerts</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam 3015CN, The Netherlands." href="#full-view-affiliation-7" ref="linksrc=author_aff">
7
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30
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
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1
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data-ga-label="Olafur A Stefansson">Olafur A Stefansson</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Cancer Research Laboratory, Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland." href="#full-view-affiliation-31" ref="linksrc=author_aff">
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1
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data-ga-label="Isabelle Treilleux">Isabelle Treilleux</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, Centre Léon Bérard, 28 rue Laënnec, 69373 Lyon Cédex 08, France." href="#full-view-affiliation-33" ref="linksrc=author_aff">
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18
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, GZA Hospitals Sint-Augustinus, Antwerp, Belgium." href="#full-view-affiliation-34" ref="linksrc=author_aff">
34
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18
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, GZA Hospitals Sint-Augustinus, Antwerp, Belgium." href="#full-view-affiliation-34" ref="linksrc=author_aff">
34
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
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36
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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16
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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37
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, London SW3 6JB, UK." href="#full-view-affiliation-38" ref="linksrc=author_aff">
38
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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39
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway." href="#full-view-affiliation-40" ref="linksrc=author_aff">
40
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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41
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Singapore General Hospital, Outram Road, 169608, Singapore." href="#full-view-affiliation-42" ref="linksrc=author_aff">
42
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16
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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3
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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24
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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17
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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43
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Synergie Lyon Cancer, Centre Léon Bérard, 28 rue Laënnec, Lyon Cedex 08, France." href="#full-view-affiliation-44" ref="linksrc=author_aff">
44
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1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Genomic Medicine, UT MD Anderson Cancer Center, Houston, Texas 77230, USA." href="#full-view-affiliation-45" ref="linksrc=author_aff">
45
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
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46
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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18
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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30
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Pathology Queensland, The Royal Brisbane and Women&#x27;s Hospital, Brisbane, Queensland 4029, Australia." href="#full-view-affiliation-47" ref="linksrc=author_aff">
47
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31
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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28
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, Texas 77030, USA." href="#full-view-affiliation-48" ref="linksrc=author_aff">
48
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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9
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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8
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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20
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7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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10
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="K. G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo 0310, Norway." href="#full-view-affiliation-11" ref="linksrc=author_aff">
11
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Andrea L Richardson">Andrea L Richardson</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, Brigham and Women&#x27;s Hospital, Boston, Massachusetts 02115, USA." href="#full-view-affiliation-15" ref="linksrc=author_aff">
15
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA." href="#full-view-affiliation-19" ref="linksrc=author_aff">
19
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Gu Kong">Gu Kong</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, College of Medicine, Hanyang University, Seoul 133-791, South Korea." href="#full-view-affiliation-22" ref="linksrc=author_aff">
22
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Gilles Thomas">Gilles Thomas</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Synergie Lyon Cancer, Centre Léon Bérard, 28 rue Laënnec, Lyon Cedex 08, France." href="#full-view-affiliation-44" ref="linksrc=author_aff">
44
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data-ga-label="Michael R Stratton">Michael R Stratton</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK." href="#full-view-affiliation-1" ref="linksrc=author_aff">
1
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Affiliations
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<ul class="item-list">
<li data-affiliation-id="full-view-affiliation-1"
id="full-view-affiliation-1"
><sup class="key">1</sup> Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.</li>
<li data-affiliation-id="full-view-affiliation-2"
id="full-view-affiliation-2"
><sup class="key">2</sup> East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 9NB, UK.</li>
<li data-affiliation-id="full-view-affiliation-3"
id="full-view-affiliation-3"
><sup class="key">3</sup> Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund SE-223 81, Sweden.</li>
<li data-affiliation-id="full-view-affiliation-4"
id="full-view-affiliation-4"
><sup class="key">4</sup> Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los Alamos, NM 87545, New Mexico, USA.</li>
<li data-affiliation-id="full-view-affiliation-5"
id="full-view-affiliation-5"
><sup class="key">5</sup> Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.</li>
<li data-affiliation-id="full-view-affiliation-6"
id="full-view-affiliation-6"
><sup class="key">6</sup> Department of Human Genetics, University of Leuven, B-3000 Leuven, Belgium.</li>
<li data-affiliation-id="full-view-affiliation-7"
id="full-view-affiliation-7"
><sup class="key">7</sup> Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam 3015CN, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-8"
id="full-view-affiliation-8"
><sup class="key">8</sup> Radboud University, Department of Molecular Biology, Faculty of Science, 6525GA Nijmegen, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-9"
id="full-view-affiliation-9"
><sup class="key">9</sup> European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</li>
<li data-affiliation-id="full-view-affiliation-10"
id="full-view-affiliation-10"
><sup class="key">10</sup> Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo 0310, Norway.</li>
<li data-affiliation-id="full-view-affiliation-11"
id="full-view-affiliation-11"
><sup class="key">11</sup> K. G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo 0310, Norway.</li>
<li data-affiliation-id="full-view-affiliation-12"
id="full-view-affiliation-12"
><sup class="key">12</sup> Department of Computer Science, University of Oslo, Oslo, Norway.</li>
<li data-affiliation-id="full-view-affiliation-13"
id="full-view-affiliation-13"
><sup class="key">13</sup> Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon, South Korea.</li>
<li data-affiliation-id="full-view-affiliation-14"
id="full-view-affiliation-14"
><sup class="key">14</sup> Translational Research Lab, Centre Léon Bérard, 28, rue Laënnec, 69373 Lyon Cedex 08, France.</li>
<li data-affiliation-id="full-view-affiliation-15"
id="full-view-affiliation-15"
><sup class="key">15</sup> Department of Pathology, Brigham and Women&#x27;s Hospital, Boston, Massachusetts 02115, USA.</li>
<li data-affiliation-id="full-view-affiliation-16"
id="full-view-affiliation-16"
><sup class="key">16</sup> The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-17"
id="full-view-affiliation-17"
><sup class="key">17</sup> Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Institut Jules Bordet, Bd de Waterloo 121, B-1000 Brussels, Belgium.</li>
<li data-affiliation-id="full-view-affiliation-18"
id="full-view-affiliation-18"
><sup class="key">18</sup> Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.</li>
<li data-affiliation-id="full-view-affiliation-19"
id="full-view-affiliation-19"
><sup class="key">19</sup> Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.</li>
<li data-affiliation-id="full-view-affiliation-20"
id="full-view-affiliation-20"
><sup class="key">20</sup> Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-21"
id="full-view-affiliation-21"
><sup class="key">21</sup> Department of Pathology, Asan Medical Center, College of Medicine, Ulsan University, Ulsan, South Korea.</li>
<li data-affiliation-id="full-view-affiliation-22"
id="full-view-affiliation-22"
><sup class="key">22</sup> Department of Pathology, College of Medicine, Hanyang University, Seoul 133-791, South Korea.</li>
<li data-affiliation-id="full-view-affiliation-23"
id="full-view-affiliation-23"
><sup class="key">23</sup> Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.</li>
<li data-affiliation-id="full-view-affiliation-24"
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><sup class="key">24</sup> Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard., Houston, Texas 77030, USA.</li>
<li data-affiliation-id="full-view-affiliation-25"
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><sup class="key">25</sup> Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul, South Korea.</li>
<li data-affiliation-id="full-view-affiliation-26"
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><sup class="key">26</sup> Institut National du Cancer, Research Division, Clinical Research Department, 52 avenue Morizet, 92513 Boulogne-Billancourt, France.</li>
<li data-affiliation-id="full-view-affiliation-27"
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><sup class="key">27</sup> University Hospital of Minjoz, INSERM UMR 1098, Bd Fleming, Besançon 25000, France.</li>
<li data-affiliation-id="full-view-affiliation-28"
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><sup class="key">28</sup> Pathology Department, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.</li>
<li data-affiliation-id="full-view-affiliation-29"
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><sup class="key">29</sup> Oncologie Sénologie, ICM Institut Régional du Cancer, Montpellier, France.</li>
<li data-affiliation-id="full-view-affiliation-30"
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><sup class="key">30</sup> The University of Queensland, UQ Centre for Clinical Research and School of Medicine, Brisbane, Queensland 4029, Australia.</li>
<li data-affiliation-id="full-view-affiliation-31"
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><sup class="key">31</sup> Cancer Research Laboratory, Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.</li>
<li data-affiliation-id="full-view-affiliation-32"
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><sup class="key">32</sup> IRCCS Istituto Tumori &quot;Giovanni Paolo II&quot;, Bari, Italy.</li>
<li data-affiliation-id="full-view-affiliation-33"
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><sup class="key">33</sup> Department of Pathology, Centre Léon Bérard, 28 rue Laënnec, 69373 Lyon Cédex 08, France.</li>
<li data-affiliation-id="full-view-affiliation-34"
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><sup class="key">34</sup> Department of Pathology, GZA Hospitals Sint-Augustinus, Antwerp, Belgium.</li>
<li data-affiliation-id="full-view-affiliation-35"
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><sup class="key">35</sup> Institut Curie, Paris Sciences Lettres University, Department of Pathology and INSERM U934, 26 rue d&#x27;Ulm, 75248 Paris Cedex 05, France.</li>
<li data-affiliation-id="full-view-affiliation-36"
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><sup class="key">36</sup> Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.</li>
<li data-affiliation-id="full-view-affiliation-37"
id="full-view-affiliation-37"
><sup class="key">37</sup> Breast Cancer Now Research Unit, King&#x27;s College London, London SE1 9RT, UK.</li>
<li data-affiliation-id="full-view-affiliation-38"
id="full-view-affiliation-38"
><sup class="key">38</sup> Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, London SW3 6JB, UK.</li>
<li data-affiliation-id="full-view-affiliation-39"
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><sup class="key">39</sup> Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.</li>
<li data-affiliation-id="full-view-affiliation-40"
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><sup class="key">40</sup> Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway.</li>
<li data-affiliation-id="full-view-affiliation-41"
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><sup class="key">41</sup> National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore.</li>
<li data-affiliation-id="full-view-affiliation-42"
id="full-view-affiliation-42"
><sup class="key">42</sup> Singapore General Hospital, Outram Road, 169608, Singapore.</li>
<li data-affiliation-id="full-view-affiliation-43"
id="full-view-affiliation-43"
><sup class="key">43</sup> Equipe Erable, INRIA Grenoble-Rhône-Alpes, 655, Avenue de l&#x27;Europe, 38330 Montbonnot-Saint Martin, France.</li>
<li data-affiliation-id="full-view-affiliation-44"
id="full-view-affiliation-44"
><sup class="key">44</sup> Synergie Lyon Cancer, Centre Léon Bérard, 28 rue Laënnec, Lyon Cedex 08, France.</li>
<li data-affiliation-id="full-view-affiliation-45"
id="full-view-affiliation-45"
><sup class="key">45</sup> Department of Genomic Medicine, UT MD Anderson Cancer Center, Houston, Texas 77230, USA.</li>
<li data-affiliation-id="full-view-affiliation-46"
id="full-view-affiliation-46"
><sup class="key">46</sup> Department of Radiation Oncology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen 6525GA, The Netherlands.</li>
<li data-affiliation-id="full-view-affiliation-47"
id="full-view-affiliation-47"
><sup class="key">47</sup> Pathology Queensland, The Royal Brisbane and Women&#x27;s Hospital, Brisbane, Queensland 4029, Australia.</li>
<li data-affiliation-id="full-view-affiliation-48"
id="full-view-affiliation-48"
><sup class="key">48</sup> Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, Texas 77030, USA.</li>
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Landscape of somatic mutations in 560 breast cancer whole-genome sequences
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<span class="authors-list-item "><span class="full-name">Serena Nik-Zainal</span><span class="citation-separator">&nbsp;et al.</span></span>
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<span class="authors-list-item "><a class="full-name"
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1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 9NB, UK." href="#short-view-affiliation-2" ref="linksrc=author_aff">
2
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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3
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Manasa Ramakrishna">Manasa Ramakrishna</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Xueqing Zou">Xueqing Zou</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los Alamos, NM 87545, New Mexico, USA." href="#short-view-affiliation-4" ref="linksrc=author_aff">
4
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA." href="#short-view-affiliation-5" ref="linksrc=author_aff">
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Human Genetics, University of Leuven, B-3000 Leuven, Belgium." href="#short-view-affiliation-6" ref="linksrc=author_aff">
6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Arie B Brinkman">Arie B Brinkman</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Radboud University, Department of Molecular Biology, Faculty of Science, 6525GA Nijmegen, The Netherlands." href="#short-view-affiliation-8" ref="linksrc=author_aff">
8
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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9
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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10
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="K. G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo 0310, Norway." href="#short-view-affiliation-11" ref="linksrc=author_aff">
11
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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11
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Computer Science, University of Oslo, Oslo, Norway." href="#short-view-affiliation-12" ref="linksrc=author_aff">
12
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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10
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="K. G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo 0310, Norway." href="#short-view-affiliation-11" ref="linksrc=author_aff">
11
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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3
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Sung-Min Ahn">Sung-Min Ahn</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon, South Korea." href="#short-view-affiliation-13" ref="linksrc=author_aff">
13
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14
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Jane E Brock">Jane E Brock</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, Brigham and Women&#x27;s Hospital, Boston, Massachusetts 02115, USA." href="#short-view-affiliation-15" ref="linksrc=author_aff">
15
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Annegien Broeks">Annegien Broeks</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands." href="#short-view-affiliation-16" ref="linksrc=author_aff">
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1
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data-ga-label="Christine Desmedt">Christine Desmedt</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Institut Jules Bordet, Bd de Waterloo 121, B-1000 Brussels, Belgium." href="#short-view-affiliation-17" ref="linksrc=author_aff">
17
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Luc Dirix">Luc Dirix</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium." href="#short-view-affiliation-18" ref="linksrc=author_aff">
18
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
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</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="John A Foekens">John A Foekens</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam 3015CN, The Netherlands." href="#short-view-affiliation-7" ref="linksrc=author_aff">
7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
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data-ga-label="Gerrit K J Hooijer">Gerrit K J Hooijer</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands." href="#short-view-affiliation-20" ref="linksrc=author_aff">
20
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Se Jin Jang">Se Jin Jang</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, Asan Medical Center, College of Medicine, Ulsan University, Ulsan, South Korea." href="#short-view-affiliation-21" ref="linksrc=author_aff">
21
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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22
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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23
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24
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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21
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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25
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
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1
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1
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1
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1
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26
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data-ga-label="Xavier Pivot">Xavier Pivot</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="University Hospital of Minjoz, INSERM UMR 1098, Bd Fleming, Besançon 25000, France." href="#short-view-affiliation-27" ref="linksrc=author_aff">
27
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28
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1
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1
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data-ga-label="F Germán Rodríguez-González">F Germán Rodríguez-González</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam 3015CN, The Netherlands." href="#short-view-affiliation-7" ref="linksrc=author_aff">
7
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data-ga-label="Gilles Romieu">Gilles Romieu</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Oncologie Sénologie, ICM Institut Régional du Cancer, Montpellier, France." href="#short-view-affiliation-29" ref="linksrc=author_aff">
29
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data-ga-label="Anieta M Sieuwerts">Anieta M Sieuwerts</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam 3015CN, The Netherlands." href="#short-view-affiliation-7" ref="linksrc=author_aff">
7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Peter T Simpson">Peter T Simpson</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The University of Queensland, UQ Centre for Clinical Research and School of Medicine, Brisbane, Queensland 4029, Australia." href="#short-view-affiliation-30" ref="linksrc=author_aff">
30
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
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1
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data-ga-label="Olafur A Stefansson">Olafur A Stefansson</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Cancer Research Laboratory, Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland." href="#short-view-affiliation-31" ref="linksrc=author_aff">
31
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1
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32
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data-ga-label="Isabelle Treilleux">Isabelle Treilleux</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, Centre Léon Bérard, 28 rue Laënnec, 69373 Lyon Cédex 08, France." href="#short-view-affiliation-33" ref="linksrc=author_aff">
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data-ga-label="Gert G Van den Eynden">Gert G Van den Eynden</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium." href="#short-view-affiliation-18" ref="linksrc=author_aff">
18
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, GZA Hospitals Sint-Augustinus, Antwerp, Belgium." href="#short-view-affiliation-34" ref="linksrc=author_aff">
34
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Peter Vermeulen">Peter Vermeulen</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium." href="#short-view-affiliation-18" ref="linksrc=author_aff">
18
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, GZA Hospitals Sint-Augustinus, Antwerp, Belgium." href="#short-view-affiliation-34" ref="linksrc=author_aff">
34
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Vincent-Salomon+A&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
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data-ga-label="Anne Vincent-Salomon">Anne Vincent-Salomon</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Institut Curie, Paris Sciences Lettres University, Department of Pathology and INSERM U934, 26 rue d&#x27;Ulm, 75248 Paris Cedex 05, France." href="#short-view-affiliation-35" ref="linksrc=author_aff">
35
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Yates+L&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
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data-ga-label="Lucy Yates">Lucy Yates</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Caldas+C&amp;cauthor_id=27135926"
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data-ga-label="Carlos Caldas">Carlos Caldas</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK." href="#short-view-affiliation-36" ref="linksrc=author_aff">
36
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=van%27t+Veer+L&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
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data-ga-label="Laura van&#x27;t Veer">Laura van&#x27;t Veer</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands." href="#short-view-affiliation-16" ref="linksrc=author_aff">
16
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Tutt+A&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
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data-ga-label="Andrew Tutt">Andrew Tutt</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Breast Cancer Now Research Unit, King&#x27;s College London, London SE1 9RT, UK." href="#short-view-affiliation-37" ref="linksrc=author_aff">
37
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, London SW3 6JB, UK." href="#short-view-affiliation-38" ref="linksrc=author_aff">
38
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Knappskog+S&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
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data-ga-label="Stian Knappskog">Stian Knappskog</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Clinical Science, University of Bergen, 5020 Bergen, Norway." href="#short-view-affiliation-39" ref="linksrc=author_aff">
39
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway." href="#short-view-affiliation-40" ref="linksrc=author_aff">
40
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Tan+BK&amp;cauthor_id=27135926"
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data-ga-label="Benita Kiat Tee Tan">Benita Kiat Tee Tan</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore." href="#short-view-affiliation-41" ref="linksrc=author_aff">
41
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Singapore General Hospital, Outram Road, 169608, Singapore." href="#short-view-affiliation-42" ref="linksrc=author_aff">
42
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Jonkers+J&amp;cauthor_id=27135926"
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data-ga-label="Jos Jonkers">Jos Jonkers</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands." href="#short-view-affiliation-16" ref="linksrc=author_aff">
16
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Borg+%C3%85&amp;cauthor_id=27135926"
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data-ga-label="Åke Borg">Åke Borg</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund SE-223 81, Sweden." href="#short-view-affiliation-3" ref="linksrc=author_aff">
3
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Ueno+NT&amp;cauthor_id=27135926"
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data-ga-label="Naoto T Ueno">Naoto T Ueno</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard., Houston, Texas 77030, USA." href="#short-view-affiliation-24" ref="linksrc=author_aff">
24
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Sotiriou+C&amp;cauthor_id=27135926"
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data-ga-label="Christos Sotiriou">Christos Sotiriou</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Institut Jules Bordet, Bd de Waterloo 121, B-1000 Brussels, Belgium." href="#short-view-affiliation-17" ref="linksrc=author_aff">
17
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Viari+A&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
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data-ga-label="Alain Viari">Alain Viari</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Equipe Erable, INRIA Grenoble-Rhône-Alpes, 655, Avenue de l&#x27;Europe, 38330 Montbonnot-Saint Martin, France." href="#short-view-affiliation-43" ref="linksrc=author_aff">
43
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Synergie Lyon Cancer, Centre Léon Bérard, 28 rue Laënnec, Lyon Cedex 08, France." href="#short-view-affiliation-44" ref="linksrc=author_aff">
44
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Futreal+PA&amp;cauthor_id=27135926"
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data-ga-label="P Andrew Futreal">P Andrew Futreal</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Genomic Medicine, UT MD Anderson Cancer Center, Houston, Texas 77230, USA." href="#short-view-affiliation-45" ref="linksrc=author_aff">
45
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Campbell+PJ&amp;cauthor_id=27135926"
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data-ga-label="Peter J Campbell">Peter J Campbell</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Span+PN&amp;cauthor_id=27135926"
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data-ga-label="Paul N Span">Paul N Span</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Radiation Oncology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen 6525GA, The Netherlands." href="#short-view-affiliation-46" ref="linksrc=author_aff">
46
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Van+Laere+S&amp;cauthor_id=27135926"
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data-ga-label="Steven Van Laere">Steven Van Laere</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium." href="#short-view-affiliation-18" ref="linksrc=author_aff">
18
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Lakhani+SR&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
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data-ga-label="Sunil R Lakhani">Sunil R Lakhani</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="The University of Queensland, UQ Centre for Clinical Research and School of Medicine, Brisbane, Queensland 4029, Australia." href="#short-view-affiliation-30" ref="linksrc=author_aff">
30
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Pathology Queensland, The Royal Brisbane and Women&#x27;s Hospital, Brisbane, Queensland 4029, Australia." href="#short-view-affiliation-47" ref="linksrc=author_aff">
47
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Eyfjord+JE&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
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data-ga-label="Jorunn E Eyfjord">Jorunn E Eyfjord</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Cancer Research Laboratory, Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland." href="#short-view-affiliation-31" ref="linksrc=author_aff">
31
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Thompson+AM&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
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data-ga-label="Alastair M Thompson">Alastair M Thompson</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Pathology Department, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK." href="#short-view-affiliation-28" ref="linksrc=author_aff">
28
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, Texas 77030, USA." href="#short-view-affiliation-48" ref="linksrc=author_aff">
48
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Birney+E&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
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data-ga-label="Ewan Birney">Ewan Birney</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK." href="#short-view-affiliation-9" ref="linksrc=author_aff">
9
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Stunnenberg+HG&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
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data-ga-label="Hendrik G Stunnenberg">Hendrik G Stunnenberg</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Radboud University, Department of Molecular Biology, Faculty of Science, 6525GA Nijmegen, The Netherlands." href="#short-view-affiliation-8" ref="linksrc=author_aff">
8
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=van+de+Vijver+MJ&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
data-ga-category="search"
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data-ga-label="Marc J van de Vijver">Marc J van de Vijver</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands." href="#short-view-affiliation-20" ref="linksrc=author_aff">
20
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Martens+JW&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="John W M Martens">John W M Martens</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam 3015CN, The Netherlands." href="#short-view-affiliation-7" ref="linksrc=author_aff">
7
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=B%C3%B8rresen-Dale+AL&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Anne-Lise Børresen-Dale">Anne-Lise Børresen-Dale</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo 0310, Norway." href="#short-view-affiliation-10" ref="linksrc=author_aff">
10
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="K. G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo 0310, Norway." href="#short-view-affiliation-11" ref="linksrc=author_aff">
11
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Richardson+AL&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
data-ga-category="search"
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data-ga-label="Andrea L Richardson">Andrea L Richardson</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, Brigham and Women&#x27;s Hospital, Boston, Massachusetts 02115, USA." href="#short-view-affiliation-15" ref="linksrc=author_aff">
15
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA." href="#short-view-affiliation-19" ref="linksrc=author_aff">
19
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Kong+G&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Gu Kong">Gu Kong</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, College of Medicine, Hanyang University, Seoul 133-791, South Korea." href="#short-view-affiliation-22" ref="linksrc=author_aff">
22
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Thomas+G&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Gilles Thomas">Gilles Thomas</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Synergie Lyon Cancer, Centre Léon Bérard, 28 rue Laënnec, Lyon Cedex 08, France." href="#short-view-affiliation-44" ref="linksrc=author_aff">
44
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
href="/?term=Stratton+MR&amp;cauthor_id=27135926"
ref="linksrc=author_name_link"
data-ga-category="search"
data-ga-action="author_link"
data-ga-label="Michael R Stratton">Michael R Stratton</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a></sup></span>
</div>
</div>
<div class="affiliations">
<h3 class="title">
Affiliations
</h3>
<ul class="item-list">
<li data-affiliation-id="short-view-affiliation-1"
id="short-view-affiliation-1"
><sup class="key">1</sup> Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.</li>
<li data-affiliation-id="short-view-affiliation-2"
id="short-view-affiliation-2"
><sup class="key">2</sup> East Anglian Medical Genetics Service, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 9NB, UK.</li>
<li data-affiliation-id="short-view-affiliation-3"
id="short-view-affiliation-3"
><sup class="key">3</sup> Division of Oncology and Pathology, Department of Clinical Sciences Lund, Lund University, Lund SE-223 81, Sweden.</li>
<li data-affiliation-id="short-view-affiliation-4"
id="short-view-affiliation-4"
><sup class="key">4</sup> Theoretical Biology and Biophysics (T-6), Los Alamos National Laboratory, Los Alamos, NM 87545, New Mexico, USA.</li>
<li data-affiliation-id="short-view-affiliation-5"
id="short-view-affiliation-5"
><sup class="key">5</sup> Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.</li>
<li data-affiliation-id="short-view-affiliation-6"
id="short-view-affiliation-6"
><sup class="key">6</sup> Department of Human Genetics, University of Leuven, B-3000 Leuven, Belgium.</li>
<li data-affiliation-id="short-view-affiliation-7"
id="short-view-affiliation-7"
><sup class="key">7</sup> Department of Medical Oncology, Erasmus MC Cancer Institute and Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam 3015CN, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-8"
id="short-view-affiliation-8"
><sup class="key">8</sup> Radboud University, Department of Molecular Biology, Faculty of Science, 6525GA Nijmegen, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-9"
id="short-view-affiliation-9"
><sup class="key">9</sup> European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.</li>
<li data-affiliation-id="short-view-affiliation-10"
id="short-view-affiliation-10"
><sup class="key">10</sup> Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Oslo 0310, Norway.</li>
<li data-affiliation-id="short-view-affiliation-11"
id="short-view-affiliation-11"
><sup class="key">11</sup> K. G. Jebsen Centre for Breast Cancer Research, Institute for Clinical Medicine, University of Oslo, Oslo 0310, Norway.</li>
<li data-affiliation-id="short-view-affiliation-12"
id="short-view-affiliation-12"
><sup class="key">12</sup> Department of Computer Science, University of Oslo, Oslo, Norway.</li>
<li data-affiliation-id="short-view-affiliation-13"
id="short-view-affiliation-13"
><sup class="key">13</sup> Gachon Institute of Genome Medicine and Science, Gachon University Gil Medical Center, Incheon, South Korea.</li>
<li data-affiliation-id="short-view-affiliation-14"
id="short-view-affiliation-14"
><sup class="key">14</sup> Translational Research Lab, Centre Léon Bérard, 28, rue Laënnec, 69373 Lyon Cedex 08, France.</li>
<li data-affiliation-id="short-view-affiliation-15"
id="short-view-affiliation-15"
><sup class="key">15</sup> Department of Pathology, Brigham and Women&#x27;s Hospital, Boston, Massachusetts 02115, USA.</li>
<li data-affiliation-id="short-view-affiliation-16"
id="short-view-affiliation-16"
><sup class="key">16</sup> The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-17"
id="short-view-affiliation-17"
><sup class="key">17</sup> Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Institut Jules Bordet, Bd de Waterloo 121, B-1000 Brussels, Belgium.</li>
<li data-affiliation-id="short-view-affiliation-18"
id="short-view-affiliation-18"
><sup class="key">18</sup> Translational Cancer Research Unit, Center for Oncological Research, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.</li>
<li data-affiliation-id="short-view-affiliation-19"
id="short-view-affiliation-19"
><sup class="key">19</sup> Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.</li>
<li data-affiliation-id="short-view-affiliation-20"
id="short-view-affiliation-20"
><sup class="key">20</sup> Department of Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-21"
id="short-view-affiliation-21"
><sup class="key">21</sup> Department of Pathology, Asan Medical Center, College of Medicine, Ulsan University, Ulsan, South Korea.</li>
<li data-affiliation-id="short-view-affiliation-22"
id="short-view-affiliation-22"
><sup class="key">22</sup> Department of Pathology, College of Medicine, Hanyang University, Seoul 133-791, South Korea.</li>
<li data-affiliation-id="short-view-affiliation-23"
id="short-view-affiliation-23"
><sup class="key">23</sup> Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.</li>
<li data-affiliation-id="short-view-affiliation-24"
id="short-view-affiliation-24"
><sup class="key">24</sup> Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard., Houston, Texas 77030, USA.</li>
<li data-affiliation-id="short-view-affiliation-25"
id="short-view-affiliation-25"
><sup class="key">25</sup> Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul, South Korea.</li>
<li data-affiliation-id="short-view-affiliation-26"
id="short-view-affiliation-26"
><sup class="key">26</sup> Institut National du Cancer, Research Division, Clinical Research Department, 52 avenue Morizet, 92513 Boulogne-Billancourt, France.</li>
<li data-affiliation-id="short-view-affiliation-27"
id="short-view-affiliation-27"
><sup class="key">27</sup> University Hospital of Minjoz, INSERM UMR 1098, Bd Fleming, Besançon 25000, France.</li>
<li data-affiliation-id="short-view-affiliation-28"
id="short-view-affiliation-28"
><sup class="key">28</sup> Pathology Department, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.</li>
<li data-affiliation-id="short-view-affiliation-29"
id="short-view-affiliation-29"
><sup class="key">29</sup> Oncologie Sénologie, ICM Institut Régional du Cancer, Montpellier, France.</li>
<li data-affiliation-id="short-view-affiliation-30"
id="short-view-affiliation-30"
><sup class="key">30</sup> The University of Queensland, UQ Centre for Clinical Research and School of Medicine, Brisbane, Queensland 4029, Australia.</li>
<li data-affiliation-id="short-view-affiliation-31"
id="short-view-affiliation-31"
><sup class="key">31</sup> Cancer Research Laboratory, Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.</li>
<li data-affiliation-id="short-view-affiliation-32"
id="short-view-affiliation-32"
><sup class="key">32</sup> IRCCS Istituto Tumori &quot;Giovanni Paolo II&quot;, Bari, Italy.</li>
<li data-affiliation-id="short-view-affiliation-33"
id="short-view-affiliation-33"
><sup class="key">33</sup> Department of Pathology, Centre Léon Bérard, 28 rue Laënnec, 69373 Lyon Cédex 08, France.</li>
<li data-affiliation-id="short-view-affiliation-34"
id="short-view-affiliation-34"
><sup class="key">34</sup> Department of Pathology, GZA Hospitals Sint-Augustinus, Antwerp, Belgium.</li>
<li data-affiliation-id="short-view-affiliation-35"
id="short-view-affiliation-35"
><sup class="key">35</sup> Institut Curie, Paris Sciences Lettres University, Department of Pathology and INSERM U934, 26 rue d&#x27;Ulm, 75248 Paris Cedex 05, France.</li>
<li data-affiliation-id="short-view-affiliation-36"
id="short-view-affiliation-36"
><sup class="key">36</sup> Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.</li>
<li data-affiliation-id="short-view-affiliation-37"
id="short-view-affiliation-37"
><sup class="key">37</sup> Breast Cancer Now Research Unit, King&#x27;s College London, London SE1 9RT, UK.</li>
<li data-affiliation-id="short-view-affiliation-38"
id="short-view-affiliation-38"
><sup class="key">38</sup> Breast Cancer Now Toby Robins Research Centre, Institute of Cancer Research, London SW3 6JB, UK.</li>
<li data-affiliation-id="short-view-affiliation-39"
id="short-view-affiliation-39"
><sup class="key">39</sup> Department of Clinical Science, University of Bergen, 5020 Bergen, Norway.</li>
<li data-affiliation-id="short-view-affiliation-40"
id="short-view-affiliation-40"
><sup class="key">40</sup> Department of Oncology, Haukeland University Hospital, 5021 Bergen, Norway.</li>
<li data-affiliation-id="short-view-affiliation-41"
id="short-view-affiliation-41"
><sup class="key">41</sup> National Cancer Centre Singapore, 11 Hospital Drive, 169610, Singapore.</li>
<li data-affiliation-id="short-view-affiliation-42"
id="short-view-affiliation-42"
><sup class="key">42</sup> Singapore General Hospital, Outram Road, 169608, Singapore.</li>
<li data-affiliation-id="short-view-affiliation-43"
id="short-view-affiliation-43"
><sup class="key">43</sup> Equipe Erable, INRIA Grenoble-Rhône-Alpes, 655, Avenue de l&#x27;Europe, 38330 Montbonnot-Saint Martin, France.</li>
<li data-affiliation-id="short-view-affiliation-44"
id="short-view-affiliation-44"
><sup class="key">44</sup> Synergie Lyon Cancer, Centre Léon Bérard, 28 rue Laënnec, Lyon Cedex 08, France.</li>
<li data-affiliation-id="short-view-affiliation-45"
id="short-view-affiliation-45"
><sup class="key">45</sup> Department of Genomic Medicine, UT MD Anderson Cancer Center, Houston, Texas 77230, USA.</li>
<li data-affiliation-id="short-view-affiliation-46"
id="short-view-affiliation-46"
><sup class="key">46</sup> Department of Radiation Oncology, Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen 6525GA, The Netherlands.</li>
<li data-affiliation-id="short-view-affiliation-47"
id="short-view-affiliation-47"
><sup class="key">47</sup> Pathology Queensland, The Royal Brisbane and Women&#x27;s Hospital, Brisbane, Queensland 4029, Australia.</li>
<li data-affiliation-id="short-view-affiliation-48"
id="short-view-affiliation-48"
><sup class="key">48</sup> Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, 1400 Pressler Street, Houston, Texas 77030, USA.</li>
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Author Correction: Landscape of somatic mutations in 560 breast cancer whole-genome sequences.
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<span class="docsum-authors full-authors">Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X, Martincorena I, Alexandrov LB, Martin S, Wedge DC, Van Loo P, Ju YS, Smid M, Brinkman AB, Morganella S, Aure MR, Lingjærde OC, Langerød A, Ringnér M, Ahn SM, Boyault S, Brock JE, Broeks A, Butler A, Desmedt C, Dirix L, Dronov S, Fatima A, Foekens JA, Gerstung M, Hooijer GKJ, Jang SJ, Jones DR, Kim HY, King TA, Krishnamurthy S, Lee HJ, Lee JY, Li Y, McLaren S, Menzies A, Mustonen V, O'Meara S, Pauporté I, Pivot X, Purdie CA, Raine K, Ramakrishnan K, Rodríguez-González FG, Romieu G, Sieuwerts AM, Simpson PT, Shepherd R, Stebbings L, Stefansson OA, Teague J, Tommasi S, Treilleux I, Van den Eynden GG, Vermeulen P, Vincent-Salomon A, Yates L, Caldas C, Van't Veer L, Tutt A, Knappskog S, Tan BKT, Jonkers J, Borg Å, Ueno NT, Sotiriou C, Viari A, Futreal PA, Campbell PJ, Span PN, Van Laere S, Lakhani SR, Eyfjord JE, Thompson AM, Birney E, Stunnenberg HG, van de Vijver MJ, Martens JWM, Børresen-Dale AL, Richardson AL, Kong G, Thomas G, Stratton MR.</span>
<span class="docsum-authors short-authors">Nik-Zainal S, et al.</span>
<span class="docsum-journal-citation full-journal-citation">Nature. 2019 Feb;566(7742):E1. doi: 10.1038/s41586-019-0883-2.</span>
<span class="docsum-journal-citation short-journal-citation">Nature. 2019.</span>
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We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.
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<p> Extended Data Figure 1. Landscape of driver… </p>
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<p> Extended Data Figure 1. Landscape of driver mutations </p>
</strong>
<div class="figure-caption-contents"><p> (A) Summary of subtypes of cohort of… </p></div>
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Extended Data Figure 1. Landscape of driver mutations
</strong>
<div class="figure-caption-contents">(A) Summary of subtypes of cohort of 560 breast cancers (B) Driver mutations by mutation type (C) Distribution of rearrangements throughout the genome. Black line represents background rearrangement density (calculation based on rearrangement breakpoints in intergenic regions only). Red lines represent frequency of rearrangement within breast cancer genes.</div>
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<p> Extended Data Figure 2. Rearrangements in oncogenes </p>
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<p> Extended Data Figure 2. Rearrangements in oncogenes </p>
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<div class="figure-caption-contents"><p> (A) Variation in rearrangement and copy number events… </p></div>
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Extended Data Figure 2. Rearrangements in oncogenes
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<div class="figure-caption-contents">(A) Variation in rearrangement and copy number events affecting <i>ESR1</i>. Clear amplification in topmost panel, transection of <i>ESR1</i> in middle panel and focused tandem duplication events in lower panel. (B) Predicted outcomes of some rearrangements affecting <i>ETV6</i>. Red crosses indicate exons deleted as a result of rearrangements within the <i>ETV6</i> genes, black dotted lines indicate rearrangement break points resulting in fusions between <i>ETV6</i> and <i>ERC, WNK1, ATP2B1</i> or <i>LRP6</i></div>
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<p> Extended Data Figure 3. Recurrent non-coding events… </p>
</strong>
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<strong class="figure-label">
<p> Extended Data Figure 3. Recurrent non-coding events in breast cancers </p>
</strong>
<div class="figure-caption-contents"><p> (A) Manhattan plot demonstrating sites… </p></div>
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Extended Data Figure 3. Recurrent non-coding events in breast cancers
</strong>
<div class="figure-caption-contents">(A) Manhattan plot demonstrating sites with most significant p-values as identified by binning analysis. Purple highlighted sites were also detected by the method seeking recurrence when partitioned by genomic features. (B) Locus at chr11:65Mb which was identified by independent analyses as being more mutated than expected by chance. In the lowermost panel, a rearrangement hotspot analysis identified this region as a tandem duplication hotspot, with nested tandem duplications noted at this site. Partitioning the genome into different regulatory elements, an analysis of substitutions and indels identified lncRNAs MALAT1 and NEAT1 (topmost panels) with significant p-values.</div>
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<strong class="figure-label">
<p> Extended Data Figure 4. Copy number analyses </p>
</strong>
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<strong class="figure-label">
<p> Extended Data Figure 4. Copy number analyses </p>
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<div class="figure-caption-contents"><p> (A) Frequency of copy number aberrations across the… </p></div>
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Extended Data Figure 4. Copy number analyses
</strong>
<div class="figure-caption-contents">(A) Frequency of copy number aberrations across the cohort. Chromosome position along x-axis, frequency of copy number gains (red) and losses (green) y-axis. (B) Identification of focal recurrent copy number gains by the GISTIC method (Supplementary Methods) (C) Identification of focal recurrent copy number losses by the GISTIC method (D) Heatmap of GISTIC regions following unsupervised hierarchical clustering. 5 cluster groups are noted and relationships with expression subtype (basal=red, luminal B=light blue, luminal A=dark blue), immunohistopathology status (ER, PR, HER2 status black=positive), abrogation of <i>BRCA1</i> (red) and <i>BRCA2</i> (blue) (whether germline, somatic or through promoter hypermethylation), driver mutations (black=positive), HRD index (top 25% or lowest 25% - black=positive).</div>
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<strong class="figure-label">
<p> Extended Data Figure 5. miRNA analyses </p>
</strong>
<div class="figure-caption-contents"><p> Hierarchical… </p></div>
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<p> Extended Data Figure 5. miRNA analyses </p>
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<div class="figure-caption-contents"><p> Hierarchical clustering of the most variant miRNAs using complete… </p></div>
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<strong class="figure-label">
Extended Data Figure 5. miRNA analyses
</strong>
<div class="figure-caption-contents">Hierarchical clustering of the most variant miRNAs using complete linkage and Euclidean distance. miRNA clusters were assigned using the Partitioning Algorithm using Recursive Thresholding (PART) method. Five main patient clusters were revealed. The horizontal annotation bars show (from top to bottom): PART cluster group, PAM50 mRNA expression subtype, GISTIC cluster, rearrangement cluster, lymphocyte infiltration score and histological grade. The heatmap shows clustered and centered miRNA expression data (log2 transformed). Details on colour coding of the annotation bars are presented below the heatmap.</div>
</figcaption>
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data-pmc-id="PMC4910866"
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<p> Extended Data Figure 6. Rearrangement cluster groups… </p>
</strong>
</div>
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Extended Data Figure 6. Rearrangement cluster groups and associated features </p>
</strong>
<div class="figure-caption-contents"><p> (A) Overall survival by rearrangement… </p></div>
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Extended Data Figure 6. Rearrangement cluster groups and associated features
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<div class="figure-caption-contents">(A) Overall survival by rearrangement cluster group (B) Age of diagnosis (C) Tumor grade (D) Menopausal status (E) ER status (F) Immune response metagene panel (G) Lymphocytic infiltration score</div>
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<p> Extended Data Figure 7. Contrasting tandem duplication… </p>
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<p> Extended Data Figure 7. Contrasting tandem duplication phenotypes </p>
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<div class="figure-caption-contents"><p> Contrasting tandem duplication phenotypes of two breast… </p></div>
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Extended Data Figure 7. Contrasting tandem duplication phenotypes
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<div class="figure-caption-contents">Contrasting tandem duplication phenotypes of two breast cancers using chromosome X. Copy number (y-axis) depicted as black dots. Lines represent rearrangements breakpoints (green=tandem duplications, pink=deletions, blue=inversions, black=translocations with partner breakpoint provided). Top panel, PD4841a, is overwhelmed by large tandem duplications (>100kb, RS1) while PD4833a has many short tandem duplications (< 10kb, RS3) appearing as single lines in its plot.</div>
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<p> Extended Data Figure 8. Hotspots of tandem… </p>
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<p> Extended Data Figure 8. Hotspots of tandem duplications </p>
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<div class="figure-caption-contents"><p> A tandem duplication hotspot occurring in 6… </p></div>
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Extended Data Figure 8. Hotspots of tandem duplications
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<div class="figure-caption-contents">A tandem duplication hotspot occurring in 6 different patients</div>
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<p> Extended Data Figure 9. Rearrangement breakpoint junctions </p>
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<p> Extended Data Figure 9. Rearrangement breakpoint junctions </p>
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<div class="figure-caption-contents"><p> (A) Breakpoint features of rearrangements in 560 breast… </p></div>
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Extended Data Figure 9. Rearrangement breakpoint junctions
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<div class="figure-caption-contents">(A) Breakpoint features of rearrangements in 560 breast cancers by Rearrangement Signature. (B) Breakpoint features in BRCA and non-BRCA cancers</div>
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<p> Extended Data Figure 10. Signatures of focal… </p>
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<p> Extended Data Figure 10. Signatures of focal hypermutation </p>
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<div class="figure-caption-contents"><p> (A) Kataegis and alternative kataegis occurring at… </p></div>
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Extended Data Figure 10. Signatures of focal hypermutation
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<div class="figure-caption-contents">(A) Kataegis and alternative kataegis occurring at the same locus (ERBB2 amplicon in PD13164a). Copy number (y-axis) depicted as black dots. Lines represent rearrangements breakpoints (green=tandem duplications, pink=deletions, blue=inversions). Topmost panel showing a ~10Mb region including the ERBB2 locus. Second panel from top zooms in 10-fold to a ~1Mb window highlighting co-occurrence of rearrangement breakpoints, with copy number changes and three different kataegis loci. Third panel from top demonstrates kataegis loci in more detail. Log10 intermutation distance on y axis. Black arrow highlighting kataegis. Blue arrows highlighting alternative kataegis. (B) Sequence context of kataegis and alternative kataegis identified in this dataset.</div>
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<img class="figure-thumb" itemprop="thumbnail"
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<p> Figure 1. Cohort and catalogue of somatic… </p>
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<p> Figure 1. Cohort and catalogue of somatic mutations in 560 breast cancers. </p>
</strong>
<div class="figure-caption-contents"><p> (A) Catalogue of… </p></div>
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Figure 1. Cohort and catalogue of somatic mutations in 560 breast cancers.
</strong>
<div class="figure-caption-contents">(A) Catalogue of base substitutions, insertions/deletions, rearrangements and driver mutations in 560 breast cancers (sorted by total substitution burden). Indel axis limited to 5,000(*). (B) Complete list of curated driver genes sorted by frequency (descending). Fraction of ER positive (left, total 366) and ER negative (right, total 194) samples carrying a mutation in the relevant driver gene presented in grey. Log10 p-value of enrichment of each driver gene towards the ER positive or ER negative cohort is provided in black. Highlighted in green are genes for which there is new or further evidence supporting these as novel breast cancer genes.</div>
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<p> Figure 2. Non-coding analyses of breast cancer… </p>
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<p> Figure 2. Non-coding analyses of breast cancer genomes </p>
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<div class="figure-caption-contents"><p> (A) Distributions of substitution (purple dots) and… </p></div>
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Figure 2. Non-coding analyses of breast cancer genomes
</strong>
<div class="figure-caption-contents">(A) Distributions of substitution (purple dots) and indel (blue dots) mutations within the footprint of five regulatory regions identified as being more significantly mutated than expected is provided on the left. The proportion of base substitution mutation signatures associated with corresponding samples carrying mutations in each of these non-coding regions, is displayed on the right. (B) Mutability of T<underline>G</underline>AA<underline>C</underline>A/T<underline>G</underline>TT<underline>C</underline>A motifs within inverted repeats of varying flanking palindromic sequence length compared to motifs not within an inverted repeat. (C) Variation in mutability between loci of TGAACA/TGTTCA inverted repeats with 9bp palindromes.</div>
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<p> Figure 3. Extraction and contributions of base… </p>
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<strong class="figure-label">
<p> Figure 3. Extraction and contributions of base substitution signatures in 560 breast cancers </p>
</strong>
<div class="figure-caption-contents"><p> (A) Twelve… </p></div>
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<strong class="figure-label">
Figure 3. Extraction and contributions of base substitution signatures in 560 breast cancers
</strong>
<div class="figure-caption-contents">(A) Twelve mutation signatures extracted using Non-Negative Matrix Factorization. Each signature is ordered by mutation class (C>A/G>T, C>G/G>C, C>T/G>A, T>A/A>T, T>C/A>G, T>G/A>C), taking immediate flanking sequence into account. For each class, mutations are ordered by 5 base (A,C,G,T) first before 3 base (A,C,G,T). (B) The spectrum of base substitution signatures within 560 breast cancers. Mutation signatures are ordered (and coloured) according to broad biological groups: Signatures 1 and 5 are correlated with age of diagnosis, Signatures 2 and 13 are putatively APOBEC-related, Signatures 6, 20 and 26 are associated with MMR deficiency, Signatures 3 and 8 are associated with HR deficiency, Signatures 18, 17 and 30 have unknown etiology. For ease of reading, this arrangement is adopted for the rest of the manuscript. Samples are ordered according to hierarchical clustering performed on mutation signatures. Top panel shows absolute numbers of mutations of each signature in each sample. Lower panel shows proportion of each signature in each sample. (C) Distribution of mutation counts for each signature in relevant breast cancer samples. Percentage of samples carrying each signature provided above each signature.</div>
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<p> Figure 4. Additional characteristics of base substitution… </p>
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<p> Figure 4. Additional characteristics of base substitution signatures and novel rearrangement signatures in 560 breast… </p>
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<strong class="figure-label">
Figure 4. Additional characteristics of base substitution signatures and novel rearrangement signatures in 560 breast cancers
</strong>
<div class="figure-caption-contents">(A) Contrasting transcriptional strand asymmetry and replication strand asymmetry between twelve base substitution signatures. (B) Six rearrangement signatures extracted using Non-Negative Matrix Factorization. Probability of rearrangement element on y-axis. Rearrangement size on x-axis. Del= deletion, tds = tandem duplication, inv = inversion, trans = translocation.</div>
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<p> Figure 5. Integrative analysis of rearrangement signatures </p>
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<p> Figure 5. Integrative analysis of rearrangement signatures </p>
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<div class="figure-caption-contents"><p> Heatmap of rearrangement signatures (RS) following unsupervised hierarchical… </p></div>
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Figure 5. Integrative analysis of rearrangement signatures
</strong>
<div class="figure-caption-contents">Heatmap of rearrangement signatures (RS) following unsupervised hierarchical clustering based on proportions of RS in each cancer. 7 cluster groups (A-G) noted and relationships with expression (AIMS) subtype (basal=red, luminal B=light blue, luminal A=dark blue), immunohistopathology status (ER, PR, HER2 status black=positive), abrogation of <i>BRCA1</i> (purple) and <i>BRCA2</i> (orange) (whether germline, somatic or through promoter hypermethylation), presence of 3 or more foci of kataegis (black=positive), HRD index (top 25% or lowest 25% - black=positive), GISTIC cluster group (black=positive) and driver mutations in cancer genes. miRNA cluster groups : 0=red, 1=purple, 2=blue, 3=light blue, 4=green, 5=orange. Contribution of base substitution signatures in these 7 cluster groups is provided in the lowermost panel.</div>
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Cancer genomics: A catalogue of somatic mutations.
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<div id="substances" class="substances keywords-section">
<h2 class="title">
Substances
</h2>
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<div id="related-links" class="related-links">
<h2 class="title">
Related information
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Cited in Books
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ClinVar
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ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=27135926&ordinalpos=1&linkpos=3">
MedGen
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MedGen (Bookshelf cited)
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OMIM (cited)
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<div id="grants" class="grants">
<h2 class="title">
Grants and funding
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<div id="linkout" class="linkout">
<h2 class="title">
LinkOut - more resources
</h2>
<ul class="linkout-list"><li><h3 class="linkout-category">Full Text Sources</h3><ul class="linkout-category-links"><li><a
href="https://europepmc.org/abstract/MED/27135926"
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Nature Publishing Group
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