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<meta name="description" content="Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A …"><meta name="keywords" content="pmid:26102509, PMC4477877, doi:10.1371/journal.pgen.1005262, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Sabine Topka, Joseph Vijai, Kenneth Offit, Amino Acid Sequence, Case-Control Studies, ETS Translocation Variant 6 Protein, Germ-Line Mutation*, HeLa Cells, Humans, Molecular Sequence Data, Mutation, Missense*, Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*, Proto-Oncogene Proteins c-ets / chemistry, Proto-Oncogene Proteins c-ets / genetics*, Proto-Oncogene Proteins c-ets / metabolism, Repressor Proteins / chemistry, Repressor Proteins / genetics*, Repressor Proteins / metabolism, Thrombocytopenia / 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="Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia - PubMed"><meta property="og:url" content="https://pubmed.ncbi.nlm.nih.gov/26102509/"><meta property="og:description" content="Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A …"><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="Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia - PubMed"><meta name="twitter:url" content="https://pubmed.ncbi.nlm.nih.gov/26102509/"><meta name="twitter:description" content="Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A …"><meta name="twitter:image" content="https://cdn.ncbi.nlm.nih.gov/pubmed/persistent/pubmed-meta-image-v2.jpg">
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|
||
<a href="/clipboard/"
|
||
class="search-input-link clipboard-link hidden"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="clipboard">
|
||
Clipboard <span class="amount-in-clipboard"></span>
|
||
</a>
|
||
</div>
|
||
|
||
<span class="search-input-link user-guide-link" role="navigation" aria-label="User guide">
|
||
<a href="/help/"
|
||
data-ga-category="featured_link"
|
||
data-ga-action="user_guide">
|
||
User Guide
|
||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F26102509%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F26102509%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="DNWxonSmoF1v4lDD0vSOnZ9j7SmlDyiTUAGC1dlIYgOZYMJtDOvQR7FXFW4xw9Qd">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-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">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="DNWxonSmoF1v4lDD0vSOnZ9j7SmlDyiTUAGC1dlIYgOZYMJtDOvQR7FXFW4xw9Qd">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</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="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="DNWxonSmoF1v4lDD0vSOnZ9j7SmlDyiTUAGC1dlIYgOZYMJtDOvQR7FXFW4xw9Qd">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 26102509 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 26102509"/>
|
||
<input type="hidden" name="email-subject-hash" value="9aab47a02ec62392d6ce19dabbc707f8f8d628e81b71fcf9d5a52bf1bd347d34"/>
|
||
</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="DNWxonSmoF1v4lDD0vSOnZ9j7SmlDyiTUAGC1dlIYgOZYMJtDOvQR7FXFW4xw9Qd">
|
||
|
||
|
||
|
||
<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="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
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/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="DNWxonSmoF1v4lDD0vSOnZ9j7SmlDyiTUAGC1dlIYgOZYMJtDOvQR7FXFW4xw9Qd">
|
||
|
||
|
||
|
||
<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="DNWxonSmoF1v4lDD0vSOnZ9j7SmlDyiTUAGC1dlIYgOZYMJtDOvQR7FXFW4xw9Qd">
|
||
|
||
<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="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</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">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="DNWxonSmoF1v4lDD0vSOnZ9j7SmlDyiTUAGC1dlIYgOZYMJtDOvQR7FXFW4xw9Qd">
|
||
|
||
|
||
|
||
<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="DNWxonSmoF1v4lDD0vSOnZ9j7SmlDyiTUAGC1dlIYgOZYMJtDOvQR7FXFW4xw9Qd">
|
||
|
||
<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="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</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="26102509">
|
||
<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://dx.plos.org/10.1371/journal.pgen.1005262"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=4656&itool=Abstract-def&log$=linkouticon&uid=26102509&db=pubmed&nlmid=101239074"
|
||
title="See full text options at Public Library of Science"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="Public Library of Science"
|
||
data-ga-label="26102509"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--journals.plos.org-resource-img-external-pgen_120x30.png" alt="Public Library of Science full text link"><span class="text">
|
||
|
||
Public Library of Science
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/26102509/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=26102509&db=pubmed&nlmid=101239074"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="26102509"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<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="/26102509/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/26102509/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="26102509" 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%2F26102509%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="DNWxonSmoF1v4lDD0vSOnZ9j7SmlDyiTUAGC1dlIYgOZYMJtDOvQR7FXFW4xw9Qd"><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"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-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-dialog-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-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
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-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
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="collections_button"
|
||
data-ga-action="click"
|
||
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="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
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Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia
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data-ga-label="Emily Quinn">Emily Quinn</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="St Jude Children's Research Hospital (SJCRH), Memphis, Tennessee, United States of America." href="#full-view-affiliation-2" ref="linksrc=author_aff">
|
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2
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|
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2
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2
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2
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2
|
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|
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2
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|
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4
|
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|
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5
|
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|
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3
|
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</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Kasmintan Schrader">Kasmintan Schrader</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="University of British Columbia, Vancouver, British Columbia, Canada." href="#full-view-affiliation-6" ref="linksrc=author_aff">
|
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6
|
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</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Anne Lincoln">Anne Lincoln</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York, United States of America." href="#full-view-affiliation-3" ref="linksrc=author_aff">
|
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3
|
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</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="James Bussel">James Bussel</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Weill Cornell Medical College, New York, New York, United States of America." href="#full-view-affiliation-7" ref="linksrc=author_aff">
|
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7
|
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|
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7
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</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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|
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8
|
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</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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5
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|
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3
|
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</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Charles Mullighan">Charles Mullighan</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="St Jude Children's Research Hospital (SJCRH), Memphis, Tennessee, United States of America." href="#full-view-affiliation-2" ref="linksrc=author_aff">
|
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2
|
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</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Michael Weintraub">Michael Weintraub</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Pediatric Hematology/Oncology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel." href="#full-view-affiliation-5" ref="linksrc=author_aff">
|
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5
|
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</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Akiko Shimamura">Akiko Shimamura</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington, United States of America; Seattle Children's Hospital, Seattle, Washington, United States of America." href="#full-view-affiliation-9" ref="linksrc=author_aff">
|
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9
|
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</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Jinghui Zhang">Jinghui Zhang</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="St Jude Children's Research Hospital (SJCRH), Memphis, Tennessee, United States of America." href="#full-view-affiliation-2" ref="linksrc=author_aff">
|
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2
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="James R Downing">James R Downing</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="St Jude Children's Research Hospital (SJCRH), Memphis, Tennessee, United States of America." href="#full-view-affiliation-2" ref="linksrc=author_aff">
|
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2
|
||
</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Kim E Nichols">Kim E Nichols</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="St Jude Children's Research Hospital (SJCRH), Memphis, Tennessee, United States of America." href="#full-view-affiliation-2" ref="linksrc=author_aff">
|
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2
|
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</a></sup><span class="comma">, </span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Kenneth Offit">Kenneth Offit</a><sup class="affiliation-links"><span class="author-sup-separator"> </span><a class="affiliation-link" title="Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York, United States of America; Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, New York, United States of America; Weill Cornell Medical College, New York, New York, United States of America." href="#full-view-affiliation-10" ref="linksrc=author_aff">
|
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10
|
||
</a></sup></span>
|
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</div>
|
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Affiliations
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|
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|
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|
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DOI:
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10.1371/journal.pgen.1005262
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<h1 class="heading-title">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia
|
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||
|
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|
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</h1>
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><sup class="key">10</sup> Department of Medicine, Memorial Sloan Kettering Cancer Center (MSKCC), New York, New York, United States of America; Cancer Biology and Genetics Program, Sloan Kettering Institute, New York, New York, United States of America; Weill Cornell Medical College, New York, New York, United States of America.</li>
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<p>
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Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition.
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The authors have declared that no competing interests exist.</p>
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Figures
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baf/4477877/88973da03e83/pgen.1005262.g001.gif"
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<strong class="figure-label">
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<p> Fig 1. Identification of germline mutations in… </p>
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<strong class="figure-label">
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<p> Fig 1. Identification of germline mutations in <i> ETV6 </i> in 2 unrelated kindreds. </p>
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<div class="figure-caption-contents"><p> (a) In Kindred… </p></div>
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Fig 1. Identification of germline mutations in <i>ETV6</i> in 2 unrelated kindreds.
|
||
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|
||
|
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|
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|
||
<div class="figure-caption-contents">(a) In Kindred 1, targeted sequencing identified a germline <i>ETV6</i> L349P mutation. Sequencing was performed on 9 individuals including the proband (arrow) affected with thrombocytopenia and/or ALL and 7 unaffected individuals as noted in Table 1. (b) In Kindred 2, clinical whole exome sequencing was performed on the proband (arrow) with ALL, MDS and AML, the mother with thrombocytopenia as well as the unaffected father. An <i>ETV6</i> N385fs mutation was identified. In both kindreds, the <i>ETV6</i> mutations segregated with disease.</div>
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<p> Fig 2. Location of somatic and germline… </p>
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<p> Fig 2. Location of somatic and germline <i> ETV6 </i> mutations and structural modeling. </p>
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Fig 2. Location of somatic and germline <i>ETV6</i> mutations and structural modeling.
|
||
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|
||
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||
|
||
<div class="figure-caption-contents">(a) Schematic depicting the germline <i>ETV6</i> mutations detected in the MSKCC and SJCRH kindred, reported separately or somatic mutations detected as part of the Pediatric Cancer Genome Project. Somatic and germline mutations are indicated by separate green and purple lines, respectively. (b) Structural modeling of ETV6 with the germline <i>ETV6</i> L349P and N385fs mutations. The <i>ETV6</i> L349P amino acid substitution is located on an α-helix within the DNA binding domain and causes extensive kinking of the protein structure. The <i>ETV6</i> N385fs mutation results in truncation of the DNA binding domain.</div>
|
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9baf/4477877/b83ab85c2c1b/pgen.1005262.g003.gif"
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<p> Fig 3. Effect of germline ETV6 mutations… </p>
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<p> Fig 3. Effect of germline ETV6 mutations on transcription. </p>
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<div class="figure-caption-contents"><p> (a) The effects of germline mutations… </p></div>
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Fig 3. Effect of germline ETV6 mutations on transcription.
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</strong>
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<div class="figure-caption-contents">(a) The effects of germline mutations on ETV6 function were examined using a Dual Luciferase Reporter Assay. Each of the mutants tested exhibited significantly (****P ≤0.0001) impaired transcriptional repression from the <i>PF4</i> and <i>MMP3</i> promoter constructs when contrasted with the WT ETV6 in the co-transfection experiment. The experiment was performed with 6 replicates for each condition and repeated 3 times. Statistical analysis was done using an unpaired t-test, the error bars show the Standard Error of Mean (SEM). (b) The effects of V37M and R181H germline mutations on ETV6 function were examined using a Dual Luciferase Reporter Assay. The experiment was performed with 6 replicates for each condition and repeated twice. Statistical analysis was done using an unpaired t-test, the error bars show the Standard Deviation (SD). (c) Quantitative PCR of ETV6 transcriptional targets <i>EGR1</i> and <i>TRAF1</i> showed reduced transcriptional abundance in the mutants when contrasted with the WT. The effect was most pronounced in the frameshift mutant. The experiment was performed in triplicate for each condition and repeated three times. Statistical analysis was done using an unpaired t-test, the error bars show the Standard Error of Mean (SEM).</div>
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data-image-alt="Fig 4"
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data-pmc-id="PMC4477877"
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data-figure-id="pgen.1005262.g004">
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alt="Fig 4" />
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<strong class="figure-label">
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<p> Fig 4. Germline <i> ETV6 </i> mutations impair localization… </p>
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</strong>
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<strong class="figure-label">
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<p> Fig 4. Germline <i> ETV6 </i> mutations impair localization of the ETV6 protein. </p>
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</strong>
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<div class="figure-caption-contents"><p> Western blots of HeLa… </p></div>
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<strong class="figure-label">
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Fig 4. Germline <i>ETV6</i> mutations impair localization of the ETV6 protein.
|
||
</strong>
|
||
|
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|
||
|
||
<div class="figure-caption-contents">Western blots of HeLa cell fractions probed for ETV6 protein show (a) presence of ETV6 within the cells transiently overexpressing ETV6 WT and the P214L, R369Q and R339C mutants within the nucleus. Both the L349P and N385fs mutant were not detected in the nuclear fraction. (b) Presence of ETV6 protein is abundant in the cytoplasmic fraction. The frameshift mutant N385fs showed a protein product that was smaller (45kDa) than the full-length protein (53kDa). (c) Densitometric analysis of the western blots shows that the WT localization is predominantly nuclear, while the L349P and N385fs are cytoplasmic. Other mutants P214L, R369Q and R339C show localization to a lesser extent in the nucleus.</div>
|
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ETV6-related thrombocytopenia: dominant negative effect of mutations as common pathogenic mechanism.
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<span class="docsum-authors full-authors">Faleschini M, Ammeti D, Papa N, Alfano C, Bottega R, Fontana G, Capaci V, Zanchetta ME, Pozzani F, Montanari F, Petroni V, Giordano P, Noris P, Giona F, Savoia A.</span>
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<span class="docsum-authors short-authors">Faleschini M, et al.</span>
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<span class="docsum-journal-citation full-journal-citation">Haematologica. 2022 Sep 1;107(9):2249-2254. doi: 10.3324/haematol.2022.280729.</span>
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<em>TP53, ETV6</em> and <em>RUNX1</em> germline variants in a case series of patients developing secondary neoplasms after treatment for childhood acute lymphoblastic leukemia.
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<span class="docsum-authors full-authors">Junk SV, Klein N, Schreek S, Zimmermann M, Möricke A, Bleckmann K, Alten J, Dagdan E, Cario G, Kratz CP, Schrappe M, Stanulla M.</span>
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<span class="docsum-authors short-authors">Junk SV, et al.</span>
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<span class="docsum-journal-citation full-journal-citation">Haematologica. 2019 Sep;104(9):e402-e405. doi: 10.3324/haematol.2018.205849. Epub 2019 Jul 9.</span>
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<span class="docsum-authors full-authors">Roberts KG, Janke LJ, Zhao Y, Seth A, Ma J, Finkelstein D, Smith S, Ebata K, Tuch BB, Hunger SP, Mullighan CG.</span>
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<span class="docsum-authors full-authors">Schick UM, Jain D, Hodonsky CJ, Morrison JV, Davis JP, Brown L, Sofer T, Conomos MP, Schurmann C, McHugh CP, Nelson SC, Vadlamudi S, Stilp A, Plantinga A, Baier L, Bien SA, Gogarten SM, Laurie CA, Taylor KD, Liu Y, Auer PL, Franceschini N, Szpiro A, Rice K, Kerr KF, Rotter JI, Hanson RL, Papanicolaou G, Rich SS, Loos RJ, Browning BL, Browning SR, Weir BS, Laurie CC, Mohlke KL, North KE, Thornton TA, Reiner AP.</span>
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<span class="docsum-journal-citation full-journal-citation">Am J Hum Genet. 2016 Feb 4;98(2):229-42. doi: 10.1016/j.ajhg.2015.12.003. Epub 2016 Jan 21.</span>
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Malkin D, Nichols KE, Zelley K, Schiffman JD (2014) Predisposition to pediatric and hematologic cancers: a moving target. Am Soc Clin Oncol Educ Book: e44-55.
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Arepally G, Rebbeck TR, Song W, Gilliland G, Maris JM, et al. (1998) Evidence for genetic homogeneity in a familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML). Blood 92: 2600–2602.
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Search in PubMed
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|
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</div>
|
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|
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|
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|
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|
||
|
||
<div id="mesh-terms" class="mesh-terms keywords-section">
|
||
<h2 class="title">
|
||
MeSH terms
|
||
</h2>
|
||
|
||
<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Amino Acid Sequence"
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Amino Acid Sequence
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</button><div id="keyword-actions-mesh-terms-0"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Amino Acid Sequence"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Amino+Acid+Sequence%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Amino+Acid+Sequence%22%5BMeSH%5D&sort=date&sort_order=desc"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Case-Control Studies"
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Case-Control Studies
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</button><div id="keyword-actions-mesh-terms-1"
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hidden
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aria-label="Dropdown menu for keyword Case-Control Studies"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Case-Control+Studies%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Case-Control+Studies%22%5BMeSH%5D&sort=date&sort_order=desc"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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ETS Translocation Variant 6 Protein
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hidden
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aria-label="Dropdown menu for keyword ETS Translocation Variant 6 Protein"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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data-href="/?term=%22ETS+Translocation+Variant+6+Protein%22%5BMeSH%5D&sort=date&sort_order=desc"
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Germ-Line Mutation*
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aria-label="Dropdown menu for keyword Germ-Line Mutation*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Search in MeSH
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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HeLa Cells
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</button><div id="keyword-actions-mesh-terms-4"
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aria-label="Dropdown menu for keyword HeLa Cells"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Humans
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</button><div id="keyword-actions-mesh-terms-5"
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aria-label="Dropdown menu for keyword Humans"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Molecular Sequence Data
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</button><div id="keyword-actions-mesh-terms-6"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Molecular Sequence Data"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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data-href="/?term=%22Molecular+Sequence+Data%22%5BMeSH%5D&sort=date&sort_order=desc"
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Search in MeSH
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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aria-label="Toggle dropdown menu for keyword Mutation, Missense*"
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tabindex="0"
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Mutation, Missense*
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</button><div id="keyword-actions-mesh-terms-major-7"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Mutation, Missense*"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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Search in PubMed
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Search in MeSH
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
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Proto-Oncogene Proteins c-ets / chemistry
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Search in PubMed
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<div id="substances" class="substances keywords-section">
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|
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|
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<div id="related-links" class="related-links">
|
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<h2 class="title">
|
||
Related information
|
||
</h2>
|
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|
||
<ul class="related-links-list"><li><a title="PubMed links associated with Books" href="https://www.ncbi.nlm.nih.gov/books?linkname=pubmed_books_refs&from_uid=26102509"
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|
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Cited in Books
|
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</a></li><li><a title="Clinical variations associated with publication" href="https://www.ncbi.nlm.nih.gov/clinvar?linkname=pubmed_clinvar&from_uid=26102509"
|
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|
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ClinVar
|
||
</a></li><li><a title="Link to related Genes" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene&from_uid=26102509"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26102509&ordinalpos=1&linkpos=3">
|
||
Gene
|
||
</a></li><li><a title="Link to Gene for the GeneRIF subcategory" href="https://www.ncbi.nlm.nih.gov/gene?linkname=pubmed_gene_rif&from_uid=26102509"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26102509&ordinalpos=1&linkpos=4">
|
||
Gene (GeneRIF)
|
||
</a></li><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&from_uid=26102509"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26102509&ordinalpos=1&linkpos=5">
|
||
MedGen
|
||
</a></li><li><a title="Related records in MedGen based on citations in GeneReviews and Medical Genetics Summaries" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen_bookshelf_cited&from_uid=26102509"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26102509&ordinalpos=1&linkpos=6">
|
||
MedGen (Bookshelf cited)
|
||
</a></li><li><a title="Link to Protein RefSeqs" href="https://www.ncbi.nlm.nih.gov/protein?linkname=pubmed_protein_refseq&from_uid=26102509"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=26102509&ordinalpos=1&linkpos=7">
|
||
Protein (RefSeq)
|
||
</a></li></ul>
|
||
</div>
|
||
|
||
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||
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||
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||
|
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Grants and funding
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