{"id":11902,"date":"2019-09-20T14:39:06","date_gmt":"2019-09-20T18:39:06","guid":{"rendered":"https:\/\/www.med.unc.edu\/biochem\/?p=11902"},"modified":"2019-11-18T14:44:24","modified_gmt":"2019-11-18T19:44:24","slug":"scientists-implicate-genes-behind-faulty-dna-repair-in-breast-cancer-2","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/biochem\/news\/scientists-implicate-genes-behind-faulty-dna-repair-in-breast-cancer-2\/","title":{"rendered":"Scientists implicate genes behind faulty DNA repair in breast cancer"},"content":{"rendered":"<p>While mutations in <em>BRCA<\/em> genes are well known to increase breast cancer risk, researchers from the University of North Carolina Lineberger Comprehensive Cancer Center have uncovered a different series of genes they believe might be contributing to breast cancer through a lesser-known mechanism.<\/p>\n<figure id=\"attachment_48238\" class=\"thumbnail wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" class=\"alignright wp-image-48238 size-medium\" src=\"https:\/\/unclineberger.org\/files\/2019\/09\/Gupta-LAB-PHOTO-300x193.jpg\" alt=\"Gaorav P. Gupta, MD, PhD, and Wanjuan Feng, PhD, postdoctoral associate at UNC Lineberger, were corresponding and first authors (respectively) of a publication in Nature Communications.\" width=\"300\" height=\"193\" \/><figcaption class=\"caption wp-caption-text\">UNC Lineberger\u2019s Gaorav P. Gupta, MD, PhD, and Wanjuan Feng, PhD, postdoctoral associate at UNC Lineberger, were corresponding and first authors (respectively) of a publication in Nature Communications.<\/figcaption><\/figure>\n<p>Mutations in <em>BRCA<\/em> cause cells to lose the ability to repair errors in DNA through a common repair mechanism, which can lead to an increase in cancer risk.<a href=\"https:\/\/www.nature.com\/articles\/s41467-019-12234-1\"> In the journal Nature Communications<\/a>, UNC Lineberger\u2019s <a href=\"https:\/\/unclineberger.org\/directory\/gaorav-gupta\/\">Gaorav P. Gupta, MD, PhD<\/a>, and colleagues report they discovered a different set of genes that could cause cells to hyper activate a more error-prone DNA repair mechanism and result in additional errors in the code.<\/p>\n<p>Their findings reveal insights as to what is driving certain types of breast cancers and provide a potential road map for future therapeutic strategies for cancers that have this hyper-activation.<\/p>\n<p>\u201cThrough our genetic screen, we were able to identify a set of genes that when altered in cells, make them highly dependent on this alternative DNA repair pathway for survival,\u201d said Gupta, assistant professor in the UNC School of Medicine Department of Radiation Oncology and Department of Biochemistry &amp; Biophysics. \u201cFuture work will explore whether targeting this pathway will lead to novel therapeutic strategies.\u201d<\/p>\n<p><strong>DNA repair and breast cancer<\/strong><\/p>\n<p>Mutations in <em>BRCA<\/em> genes can disrupt \u2013 and inactivate \u2013 a mechanism that cells use to fix breaks in their DNA. The loss of this repair mechanism can lead to cancer. Women who inherit mutations in these genes have increased risk for breast cancer.<\/p>\n<p>More recently, researchers uncovered a lesser-known mechanism of DNA repair called theta-mediated end-joining. This is a repair mechanism that researchers believe cells normally use only when they cannot use more reliable repair mechanisms. It is more error-prone, Gupta said, meaning it can lead to errors in the DNA sequence.<\/p>\n<p>\u201cUnlike <em>BRCA<\/em>, which can be inactivated in certain breast cancers, we think this pathway gets hyper-activated in tumors,\u201d Gupta said. \u201cIt\u2019s a more mutation-prone pathway that may confer advantages to tumors as they develop.\u201d<\/p>\n<p><strong>New study findings<\/strong><\/p>\n<p>In their study, Gupta and his colleagues found a series of genetic alterations they believe cause cells to become \u201caddicted\u201d to the more error-prone DNA repair pathway in order to survive.<\/p>\n<p>When they analyzed breast cancer samples from The Cancer Genome Atlas, they found about 30 percent of breast cancers in that patient group had alterations in those genes, and that these cancers had evidence, or \u201cscars,\u201d that indicated high levels of theta-mediated end-joining.<\/p>\n<p>\u201cOur work raises the possibility that these genomic scars might be useful as predictors of addiction to this polymerase theta-dependent pathway,\u201d Gupta said.<\/p>\n<p><strong>Potential treatment implications<\/strong><\/p>\n<p>Inhibitors of the polymerase theta protein that drives this form of DNA repair are in development, Gupta said.<\/p>\n<p>Given the possibility that some breast cancer cells may be relying on this error-prone pathway to fix their DNA, some scientists think the newly discovered genes could help identify which cancers might be susceptible to potential treatments that block this repair mechanism.<\/p>\n<p>\u201cThere is an open question in terms of: What are the clinical contexts in which polymerase theta inhibitors would be most effective?\u201d Gupta said. \u201cOur work begins to address this topic by identifying a set of gene mutations that may confer greater dependence on this pathway.\u201d<\/p>\n<p><em>In addition to Gupta, other authors included Wanjuan Feng, Dennis A. Simpson, Juan Carvajal-Garcia, Brandon A. Price, Rashmi J. Kumar, Lisle E. Mose, Richard D. Wood, Naim Rashid, Jeremy E. Purvis, Joel S. Parker and Dale A. Ramsden.<\/em><\/p>\n<p><em>The study was funded in part by <\/em><em>the National Cancer Institute, the Burroughs Wellcome Fund. the University Cancer Research Fund and the U.S. Department of Defense.<\/em><\/p>\n<p><em>News courtesy of Lineberger<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>While mutations in BRCA genes are well known to increase breast cancer risk, our researchers have uncovered a different series of genes they believe might be contributing to breast cancer through a lesser-known mechanism.<\/p>\n","protected":false},"author":41619,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","footnotes":"","_links_to":"","_links_to_target":""},"categories":[2],"tags":[230,10,308,233],"class_list":["post-11902","post","type-post","status-publish","format-standard","hentry","category-news","tag-2019-faculty-year-review","tag-news_faculty","tag-gaorav-p-gupta-news","tag-news_faculty_s19","odd"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Scientists implicate genes behind faulty DNA repair in breast cancer | Biochemistry and Biophysics<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/biochem\/news\/scientists-implicate-genes-behind-faulty-dna-repair-in-breast-cancer-2\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Scientists implicate genes behind faulty DNA repair in breast cancer | Biochemistry and Biophysics\" \/>\n<meta property=\"og:description\" content=\"While mutations in BRCA genes are well known to increase breast cancer risk, our researchers have uncovered a different series of genes they believe might be contributing to breast cancer through a lesser-known mechanism.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.med.unc.edu\/biochem\/news\/scientists-implicate-genes-behind-faulty-dna-repair-in-breast-cancer-2\/\" \/>\n<meta property=\"og:site_name\" content=\"Biochemistry and Biophysics\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/uncbiochemistryandbiophysics\/\" \/>\n<meta property=\"article:published_time\" content=\"2019-09-20T18:39:06+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2019-11-18T19:44:24+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/unclineberger.org\/files\/2019\/09\/Gupta-LAB-PHOTO-300x193.jpg\" \/>\n<meta name=\"author\" content=\"Carolyn Clabo\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@UNC_BCBP\" \/>\n<meta name=\"twitter:site\" content=\"@UNC_BCBP\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Carolyn Clabo\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/news\/scientists-implicate-genes-behind-faulty-dna-repair-in-breast-cancer-2\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/news\/scientists-implicate-genes-behind-faulty-dna-repair-in-breast-cancer-2\/\"},\"author\":{\"name\":\"Carolyn Clabo\",\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/#\/schema\/person\/9693a4e0a76e8208ca2105ae25587332\"},\"headline\":\"Scientists implicate genes behind faulty DNA repair in breast cancer\",\"datePublished\":\"2019-09-20T18:39:06+00:00\",\"dateModified\":\"2019-11-18T19:44:24+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/news\/scientists-implicate-genes-behind-faulty-dna-repair-in-breast-cancer-2\/\"},\"wordCount\":656,\"publisher\":{\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.med.unc.edu\/biochem\/news\/scientists-implicate-genes-behind-faulty-dna-repair-in-breast-cancer-2\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/unclineberger.org\/files\/2019\/09\/Gupta-LAB-PHOTO-300x193.jpg\",\"keywords\":[\"2019-faculty-year-review\",\"Faculty &amp; Lab News\",\"Gaorav P. 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