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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<div about="/news-events/nih-research-matters/new-gene-tied-deadly-ovarian-cancer" typeof="sioc:Item foaf:Document" class="ds-1col node node--nih-research-matters view-mode-full node--full node--nih-research-matters--full clearfix">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2010-09-20T00:00:00-04:00" class="date-display-single">September 20, 2010</span></p><div class='syndicate'><h1>New Gene Tied to Deadly Ovarian Cancer</h1><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Image of a large, round egg cell within an ovary">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2010/20100920-ovarian.jpg?itok=Ywvid1av&timestamp=1433964062 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2010/20100920-ovarian.jpg?itok=2_Z3zLpw&timestamp=1433964062 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2010/20100920-ovarian.jpg?itok=gBNwc4XD&timestamp=1433964062 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2010/20100920-ovarian.jpg?itok=KzNEGMuY&timestamp=1433964062 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2010/20100920-ovarian.jpg?itok=nkOE_Bhu&timestamp=1433964062 1x" media="screen and (min-width: 0)" />
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2010/20100920-ovarian.jpg?itok=2_Z3zLpw&timestamp=1433964062" alt="Image of a large, round egg cell within an ovary" title="Image of a large, round egg cell within an ovary" />
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</picture><span class="caption">Microscopic view of the ovary showing the central egg surrounded by protective layers of cells</span><span class="credit">Ivor Mason, King's College London. All rights reserved by Wellcome Images.</span></div>
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</div><p>Two research teams have linked an unexpected gene to an aggressive and hard-to-treat form of ovarian cancer.</p>
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<p>Ovarian cancer is the fifth deadliest cancer among women nationwide. The subtype known as ovarian clear cell carcinoma is poorly understood and can be especially resistant to standard therapy. To learn more about the genetic origins of ovarian clear cell carcinoma, 2 independent teams of scientists used different techniques to examine the exons, or protein-coding regions of the genome, in ovarian tumor cells.</p>
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<p>The first study, supported in part by NIH's National Cancer Institute (NCI), evaluated both tumor and normal cells from 8 patients who had ovarian clear cell carcinoma. A research team led by Dr. Nickolas Papadopoulos of Johns Hopkins Kimmel Cancer Center sequenced all 18,000 protein-coding genes from the cells and identified 4 that were mutated in at least 2 tumors but not in the normal cells. Of these, the most common was the gene <em>ARID1A</em>, which had never before been linked to ovarian cancer.</p>
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<p>The scientists then sequenced the 4 implicated genes in normal and tumor cells from an additional 34 patients. Most of the tumor samples had mutations in <em>ARID1A</em> (57% of the 42 tumors). Two other genes that had previously been tied to ovarian cancer—<em>PIK3CA</em> and <em>KRAS</em>—were found in 40% and 5% of the tumors, respectively. The fourth gene, <em>PPP2R1A</em>, hadn't previously been associated with ovarian cancer. It was found in 7% of the tumors.</p>
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<p>As reported in the early online issue of <em>Science</em> on September 8, 2010, the researchers conclude that <em>ARID1A</em> must act as a tumor suppressor gene. Its protein product is known to play a role in chromatin remodeling, which is a process that changes how DNA is packaged in the cell's nucleus. Chromatin remodeling can affect how and when certain genes are transcribed. When<em> ARID1A </em>is mutated, genes may be incorrectly switched on or off, which can cause cells to grow and flourish unchecked.</p>
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<p>In the second study, published that same day in the <em>New England Journal of Medicine</em>, a Canada-based research team led by Dr. David Huntsman took a slightly different approach. Rather than sequencing protein-coding DNA regions, they sequenced the transcriptome—the complete set of expressed RNAs. They analyzed different types of tumors from several tumor banks, including an NCI-funded bank at Johns Hopkins. The scientists found that the <em>ARID1A</em> gene was mutated in 46% (55 out of 119) of ovarian clear cell tumors and in 30% (10 out of 33) of endometrioid ovarian tumors, a different subtype of ovarian cancer. In contrast, the gene wasn’t altered in any of the 76 samples of a different type of ovarian tumor.</p>
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<p>Both ovarian clear cell cancer and endometrioid cancer can arise from endometriosis, a condition in which cells from the uterine lining migrate and grow in other locations, such as the ovaries. The scientists say their findings may help to shed light on molecular events that transform endometriosis into ovarian cancer.</p>
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<p>"The interesting thing about this gene [<em>ARID1A</em>] is that it's tied to something called epigenetic changes, which include changes in how the DNA is packed and regulated," says Papadopoulos. Epigenetic factors affect gene activity—in this case by altering chromatin—without altering the DNA sequence. "The next step will be to understand this pathway better," he says.</p>
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<p>—by Vicki Contie</p>
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</div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.cancer.gov/types/ovarian" target="_top">Ovarian, Fallopian Tube, and Primary Peritoneal Cancer</a></li><li><a href="https://www.nichd.nih.gov/health/topics/endometriosis" target="_top">Endometriosis</a></li><li><a href="http://www.genome.gov/27532724" target="_top">Epigenomics</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/researchers-find-value-exomes" target="_top">Researchers Find Value in Exomes</a></li></ul>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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