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<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="jgymku322Fl7XOyT57l5P33y5EP7soroA3irXkwoCg8BRfEJIqY7jbzcDIxjlZZI">
<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/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="jgymku322Fl7XOyT57l5P33y5EP7soroA3irXkwoCg8BRfEJIqY7jbzcDIxjlZZI">
<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="jgymku322Fl7XOyT57l5P33y5EP7soroA3irXkwoCg8BRfEJIqY7jbzcDIxjlZZI">
<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">
<input type="hidden" name="csrfmiddlewaretoken" value="jgymku322Fl7XOyT57l5P33y5EP7soroA3irXkwoCg8BRfEJIqY7jbzcDIxjlZZI">
<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="jgymku322Fl7XOyT57l5P33y5EP7soroA3irXkwoCg8BRfEJIqY7jbzcDIxjlZZI">
<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="30946934">
<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://linkinghub.elsevier.com/retrieve/pii/S0046-8177(19)30052-8"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=3048&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=30946934&amp;db=pubmed&amp;nlmid=9421547"
title="See full text options at Elsevier Science"
data-ga-category="full_text"
data-ga-action="Elsevier Science"
data-ga-label="30946934"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif" alt="Elsevier Science full text link"><span class="text">
Elsevier Science
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/30946934/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=30946934&amp;db=pubmed&amp;nlmid=9421547"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="30946934"
><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="/30946934/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/30946934/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="30946934" 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%2F30946934%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="jgymku322Fl7XOyT57l5P33y5EP7soroA3irXkwoCg8BRfEJIqY7jbzcDIxjlZZI"><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"
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<h1 class="heading-title">
A comparison of adult rhabdomyosarcoma and high-grade neuroendocrine carcinoma of the urinary bladder reveals novel PPP1R12A fusions in rhabdomyosarcoma
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><sup class="key">13</sup> Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065. Electronic address: reuterv@mskcc.org.</li>
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><sup class="key">14</sup> Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905. Electronic address: vasm@mayo.edu.</li>
<li data-affiliation-id="full-view-affiliation-15"
id="full-view-affiliation-15"
><sup class="key">15</sup> Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: Jimenez.Rafael@mayo.edu.</li>
<li data-affiliation-id="full-view-affiliation-16"
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><sup class="key">16</sup> Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: HerreraHernandez.Loren@mayo.edu.</li>
<li data-affiliation-id="full-view-affiliation-17"
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><sup class="key">17</sup> Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: Cheville.John@mayo.edu.</li>
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<div class="publication-type" >Comparative Study</div>
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A comparison of adult rhabdomyosarcoma and high-grade neuroendocrine carcinoma of the urinary bladder reveals novel PPP1R12A fusions in rhabdomyosarcoma
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<span class="authors-list-item "><span class="full-name">Sounak Gupta</span><span class="citation-separator">&nbsp;et al.</span></span>
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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></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></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="Kaustubh N Bhinge">Kaustubh N Bhinge</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905. Electronic address: Bhinge.Kaustubh@mayo.edu." 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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</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></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></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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11
</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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data-ga-label="Victor E Reuter">Victor E Reuter</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065. Electronic address: reuterv@mskcc.org." href="#short-view-affiliation-13" ref="linksrc=author_aff">
13
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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data-ga-label="George Vasmatzis">George Vasmatzis</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905. Electronic address: vasm@mayo.edu." href="#short-view-affiliation-14" ref="linksrc=author_aff">
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="Rafael E Jimenez">Rafael E Jimenez</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: Jimenez.Rafael@mayo.edu." 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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17
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<li data-affiliation-id="short-view-affiliation-1"
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><sup class="key">1</sup> Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: guptas1@mskcc.org.</li>
<li data-affiliation-id="short-view-affiliation-2"
id="short-view-affiliation-2"
><sup class="key">2</sup> Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: Sosa.Carlos@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-3"
id="short-view-affiliation-3"
><sup class="key">3</sup> Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905. Electronic address: Kosari.Farhad@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-4"
id="short-view-affiliation-4"
><sup class="key">4</sup> Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: folpe.andrew@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-5"
id="short-view-affiliation-5"
><sup class="key">5</sup> Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905. Electronic address: Bhinge.Kaustubh@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-6"
id="short-view-affiliation-6"
><sup class="key">6</sup> Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: Yang.Lin@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-7"
id="short-view-affiliation-7"
><sup class="key">7</sup> Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905. Electronic address: Agahi.Alireza@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-8"
id="short-view-affiliation-8"
><sup class="key">8</sup> Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905. Electronic address: Johnson.Sarah14@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-9"
id="short-view-affiliation-9"
><sup class="key">9</sup> Department of Urology, Mayo Clinic, Rochester, MN 55905. Electronic address: Frank.Igor@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-10"
id="short-view-affiliation-10"
><sup class="key">10</sup> Department of Urology, Mayo Clinic, Rochester, MN 55905. Electronic address: Boorjian.Stephen@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-11"
id="short-view-affiliation-11"
><sup class="key">11</sup> Department of Pathology, University of California at San Diego, CA 92093. Electronic address: dhansel@ucsd.edu.</li>
<li data-affiliation-id="short-view-affiliation-12"
id="short-view-affiliation-12"
><sup class="key">12</sup> Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065. Electronic address: alahmadh@mskcc.org.</li>
<li data-affiliation-id="short-view-affiliation-13"
id="short-view-affiliation-13"
><sup class="key">13</sup> Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065. Electronic address: reuterv@mskcc.org.</li>
<li data-affiliation-id="short-view-affiliation-14"
id="short-view-affiliation-14"
><sup class="key">14</sup> Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905. Electronic address: vasm@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-15"
id="short-view-affiliation-15"
><sup class="key">15</sup> Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: Jimenez.Rafael@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-16"
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><sup class="key">16</sup> Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: HerreraHernandez.Loren@mayo.edu.</li>
<li data-affiliation-id="short-view-affiliation-17"
id="short-view-affiliation-17"
><sup class="key">17</sup> Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: Cheville.John@mayo.edu.</li>
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Some rhabdomyosarcomas and sarcomatoid carcinomas with heterologous rhabdomyosarcomatous elements resemble high-grade neuroendocrine carcinoma, creating a diagnostic difficulty. The purpose of this study was to characterize the overlap of adult genitourinary rhabdomyosarcomas, excluding those occurring at paratesticular sites, with high-grade neuroendocrine carcinoma and identify features helpful in their separation. Seventeen cases of rhabdomyosarcoma (11 from the urinary bladder and 3 each from kidney and prostate) were compared to 10 cases of high-grade neuroendocrine carcinoma from the urinary bladder. These tumors were analyzed by immunohistochemistry for desmin, MyoD1, myogenin, chromogranin, synaptophysin, CD56, TTF1, and ASCL1, and RNA sequencing was performed on 4 cases of bladder rhabdomyosarcoma (2 rhabdomyosarcomas and 2 sarcomatoid-rhabdomyosarcoma) and 10 cases of bladder high-grade neuroendocrine carcinoma. This was compared to public data from 414 typical urothelial carcinomas from The Cancer Genome Atlas dataset. Morphologic and immunophenotypic overlap with high-grade neuroendocrine carcinoma was seen in half of the bladder tumors, which included 4 rhabdomyosarcomas and 2 sarcomatoid rhabdomyosarcomas. RNA sequencing confirmed expression of neuroendocrine markers in these cases (2 rhabdomyosarcomas and 2 sarcomatoid rhabdomyosarcomas). Differential neuroendocrine differentiation was highlighted by ASCL1 protein expression only in high-grade neuroendocrine carcinoma. Moreover, both a pure alveolar rhabdomyosarcoma and sarcomatoid rhabdomyosarcoma of the urinary bladder demonstrated a fusion involving PPP1R12A. In summary, adult rhabdomyosarcomas of the urinary bladder are molecularly distinct from high-grade neuroendocrine carcinomas based on specific patterns of expression of myogenic and epithelial to mesenchymal transition-related transcription factors as well as the presence of a novel PPP1R12A fusion which is seen in a subset of cases.
</p>
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<p>
<strong class="sub-title">
Keywords:
</strong>
ASCL1; Genitourinary; High-grade neuroendocrine carcinoma; PPP1R12A; Rhabdomyosarcoma; Sarcomatoid carcinoma; Urinary bladder.
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<p> Figure1:. Adult Genitourinary Rhabdomyosarcoma: Histopathology. </p>
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<div class="figure-caption-contents"><p> Representative H&amp;E… </p></div>
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<p> Figure1:. Adult Genitourinary Rhabdomyosarcoma: Histopathology. </p>
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<div class="figure-caption-contents"><p> Representative H&amp;E stained images of pure rhabdomyosarcomas of the urinary… </p></div>
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Figure1:. Adult Genitourinary Rhabdomyosarcoma: Histopathology.
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<div class="figure-caption-contents">Representative H&E stained images of pure rhabdomyosarcomas of the urinary bladder (<b>A, B</b>; 400X magnification) and a sarcomatoid carcinoma with heterologous rhabdomyosarcomatous elements showing morphologic overlap with small cell carcinoma (<b>C</b>; 400x magnification).</div>
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<p> Figure2:. Adult Genitourinary Rhabdomyosarcoma: Immunohistochemistry. </p>
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<div class="figure-caption-contents"><p> Representative images… </p></div>
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<p> Figure2:. Adult Genitourinary Rhabdomyosarcoma: Immunohistochemistry. </p>
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<div class="figure-caption-contents"><p> Representative images detailing the immunophenotype of rhabdomyosarcomas of the urinary… </p></div>
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Figure2:. Adult Genitourinary Rhabdomyosarcoma: Immunohistochemistry.
</strong>
<div class="figure-caption-contents">Representative images detailing the immunophenotype of rhabdomyosarcomas of the urinary bladder, which demonstrate morphologic overlap with small cell carcinoma (Case1: <b>A-H</b>, Case2: <b>I-P</b>, 200 X magnification). H&amp;E stained images (<b>A, I</b>), immunohistochemistry for Desmin (<b>B, J</b>), Myogenin (<b>C, K</b>), MyoD1 (<b>D, L</b>), Synaptophysin (<b>E, M</b>), Chromogranin (<b>F, N</b>), CD56 (<b>G, O</b>), and TTF1 (<b>H, P</b>) is shown.</div>
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<strong class="figure-label">
<p> Figure3:. Adult Genitourinary Rhabdomyosarcoma: Neuroendocrine Gene Expression. </p>
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<strong class="figure-label">
<p> Figure3:. Adult Genitourinary Rhabdomyosarcoma: Neuroendocrine Gene Expression. </p>
</strong>
<div class="figure-caption-contents"><p> Relative gene expression (log <sub> 2 </sub> ) for urothelial… </p></div>
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<strong class="figure-label">
Figure3:. Adult Genitourinary Rhabdomyosarcoma: Neuroendocrine Gene Expression.
</strong>
<div class="figure-caption-contents">Relative gene expression (log<sub>2</sub>) for urothelial carcinoma (n=414), high-grade neuroendocrine carcinomas (n=10), sarcomatoid carcinoma with rhabdomyosarcomatous elements (n=2) and pure rhabdomyosarcomas (n=2) for <i>PCSK1</i> (<b>A</b>), <i>SCG2</i> (<b>B</b>), <i>NCAM1</i> (<b>C</b>), <i>CHGB</i> (<b>D</b>), <i>CHGA</i> (<b>E</b>), <i>SYP</i> (<b>F</b>), <i>ASCL1</i> (<b>G</b>), and <i>INSM1</i> (<b>H</b>) is shown.</div>
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data-pmc-id="PMC8078053"
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<img class="figure-thumb" itemprop="thumbnail"
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<strong class="figure-label">
<p> Figure4:. Gene Expression of Transcriptional Regulators of… </p>
</strong>
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<strong class="figure-label">
<p> Figure4:. Gene Expression of Transcriptional Regulators of Myogenesis. </p>
</strong>
<div class="figure-caption-contents"><p> Relative gene expression (log <sub> 2 </sub> ) for… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure4:. Gene Expression of Transcriptional Regulators of Myogenesis.
</strong>
<div class="figure-caption-contents">Relative gene expression (log<sub>2</sub>) for urothelial carcinoma (n=414), high-grade neuroendocrine carcinomas (n=10), carcinoma with rhabdomyosarcomatous elements (n=2) and pure rhabdomyosarcomas
(n=2) for <i>MYOD1</i> (<b>A</b>) and <i>Myogenin</i> (<b>B</b>), <i>FOXO1</i> (<b>C</b>), <i>PAX7</i> (<b>D</b>), <i>PAX3</i> (<b>E</b>) and <i>BCOR</i> (<b>F</b>) is shown.</div>
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<p> Figure5:. Gene Expression of Transcriptional Regulators of… </p>
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<p> Figure5:. Gene Expression of Transcriptional Regulators of Epithelial to Mesenchymal Transition. </p>
</strong>
<div class="figure-caption-contents"><p> Relative gene expression (log… </p></div>
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<strong class="figure-label">
Figure5:. Gene Expression of Transcriptional Regulators of Epithelial to Mesenchymal Transition.
</strong>
<div class="figure-caption-contents">Relative gene expression (log<sub>2</sub>) for urothelial carcinoma (n=414), high-grade neuroendocrine carcinomas (n=10), carcinoma with rhabdomyosarcomatous elements (n=2) and pure rhabdomyosarcomas (n=2) for <i>ZEB1</i> (<b>A</b>) and <i>ZEB2</i> (<b>B</b>), <i>SNAI2</i> (<b>C</b>) and <i>TWIST1</i> (<b>D</b>) is shown.</div>
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<p> Figure6:. Adult Genitourinary Rhabdomyosarcoma: Immunohistochemistry, ASCL1. </p>
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<div class="figure-caption-contents"><p> Representative… </p></div>
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<strong class="figure-label">
<p> Figure6:. Adult Genitourinary Rhabdomyosarcoma: Immunohistochemistry, ASCL1. </p>
</strong>
<div class="figure-caption-contents"><p> Representative H&amp;E stained images and corresponding ASCL1 expression in… </p></div>
</div>
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure6:. Adult Genitourinary Rhabdomyosarcoma: Immunohistochemistry, ASCL1.
</strong>
<div class="figure-caption-contents">Representative H&E stained images and corresponding ASCL1 expression in a typical urothelial carcinoma (<b>A, B</b>, 200 X magnification), high-grade neuroendocrine carcinoma (<b>C, D</b>, 200 X magnification) and a pure rhabdomyosarcoma (<b>E, F</b>, 200 X magnification) is shown.</div>
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<p> Figure7:. Confirmation of <i> PPP1R12A </i> Gene Fusion in… </p>
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<strong class="figure-label">
<p> Figure7:. Confirmation of <i> PPP1R12A </i> Gene Fusion in Pure Rhabdomyosarcomas of the Bladder. </p>
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<div class="figure-caption-contents"><p> A schematic representation… </p></div>
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<strong class="figure-label">
Figure7:. Confirmation of <i>PPP1R12A</i> Gene Fusion in Pure Rhabdomyosarcomas of the Bladder.
</strong>
<div class="figure-caption-contents">A schematic representation of the <i>PPP1R12A</i>-<i>LIN7A</i> and <i>PPP1R12A</i>-<i>PTPRQ</i> structural variants has been depicted in <b>A</b>. Pyrosequencing traces demonstrate the breakpoint between exon 2 of <i>PPP1R12A</i> and exon 2 of <i>LIN7A</i> on forward (<b>B</b>) and reverse (<b>C</b>) traces. Similarly, the breakpoint between exon 10 of <i>PPP1R12A</i> and exon 4 of <i>PTPRQ</i> has been shown on both forward (<b>D</b>) and reverse (<b>E</b>) traces.</div>
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