{"id":12855,"date":"2020-02-17T12:28:52","date_gmt":"2020-02-17T17:28:52","guid":{"rendered":"https:\/\/www.med.unc.edu\/biochem\/?p=12855"},"modified":"2020-05-04T17:24:14","modified_gmt":"2020-05-04T21:24:14","slug":"researchers-implicate-gene-in-dna-errors-in-aggressive-breast-cancer","status":"publish","type":"post","link":"https:\/\/www.med.unc.edu\/biochem\/news\/researchers-implicate-gene-in-dna-errors-in-aggressive-breast-cancer\/","title":{"rendered":"Researchers implicate gene in DNA errors in aggressive breast cancer"},"content":{"rendered":"

Researchers led by UNC BCBP’s Gaorav Gupta, MD, PhD, described the role of a mutation in the Mre11 gene in triple negative breast cancer and how a disruption of Mre11 function plays a significant role in the genomic instability of that cancer type.<\/p>\n

\"\"
Gaorav Gupta, MD, PhD<\/figcaption><\/figure>\n

February 17, 2020<\/p>\n

A hallmark of triple negative breast cancer, an aggressive breast cancer type, is the accumulation of errors in the cancer cells\u2019 DNA. There are limited insights about how this so-called \u201cgenomic instability\u201d happens.<\/p>\n

In a preclinical study published in Cell Reports, researchers led by UNC Lineberger Comprehensive Cancer Center\u2019s\u00a0Gaorav Gupta, MD, PhD<\/a>, described the role of a mutation in the\u00a0Mre11<\/em>\u00a0gene in triple negative breast cancer. They found disruption of this gene\u2019s function plays a significant role in the genomic instability of triple negative breast cancer.<\/p>\n

\u201cAn extremely high level of genomic instability is a hallmark of triple negative breast cancer,\u201d said Gupta, assistant professor of radiation oncology and biochemistry & biophysics at the UNC School of Medicine. \u201cThis hallmark feature is very poorly understood, however. We wanted to ask whether mutations or alterations in DNA repair pathways may explain why they have such an unstable genome.\u201d<\/p>\n

In particular, researchers wanted to know why genomic instability occurs in triple negative breast cancers that don\u2019t have mutations in the\u00a0BRCA1<\/em>\u00a0or\u00a0BRCA2<\/em>\u00a0genes. Gupta said mutations in these genes are found in about 10 to 20 percent of triple negative breast cancers.<\/p>\n

Mutations in\u00a0BRCA1<\/em>\u00a0or\u00a0BRCA2<\/em>\u00a0can impact the cells\u2019 ability to repair breaks in their DNA. But in the absence of these mutations, researchers wanted to know how genetic errors start to accumulate and continue over time.<\/p>\n

The\u00a0Mre11<\/em>\u00a0gene codes for a \u201csensor\u201d that can detect breaks in DNA and is part of the same DNA repair pathway as\u00a0BRCA1<\/em>\u00a0and\u00a0BRCA2<\/em>, Gupta said.<\/p>\n

In mouse models of breast cancer with\u00a0Mre11\u00a0<\/em>genetic deficiencies, researchers saw a particular pattern of genomic instability and also discovered the mechanism for how deficiencies in\u00a0Mre11<\/em>\u00a0promote DNA damage.<\/p>\n

\u201cWhen we disrupted\u00a0Mre11<\/em>\u00a0in models of triple negative breast cancer, these cancerous cells were able to proliferate much faster, and they were accumulating DNA damage at a much faster rate,\u201d Gupta said. \u201cThe breast cancers that emerged in this model also exhibited a unique pattern of genomic instability that we were able to tie to this deficiency in\u00a0Mre11<\/em>.\u201d<\/p>\n

They also found triple negative breast cancers were extremely sensitive to certain drugs that act through the generation of DNA damage, like chemotherapy, and inhibitors that impair DNA repair.<\/p>\n

\u201cThese\u00a0Mre11<\/em>-deficient triple negative breast cancers were more sensitive to certain types of treatments \u2013 in particular therapies that act through generation of DNA damage,\u201d Gupta said.<\/p>\n

When the scientists stained a collection of more than 250 triple negative breast cancer samples, they found that\u00a0Mre11<\/em>\u00a0expression was lost in about 10 percent of the cases.<\/p>\n

\u201cIn the future, we would like to explore whether patients with Mre11 deficient tumors could be treated with less chemotherapy or with a targeted therapy in order to reduce toxicity and achieve higher levels of cure.\u201d<\/p>\n

In addition to Gupta, other authors include Katerina D. Fagan-Solis, Dennis A. Simpson, Rashmi J. Kumar, Luciano Martelotto, Lisle E. Mose, Naim U. Rashid, Alice Y. Ho, Simon N. Powell, Y. Hannah Wen, Joel S. Parker, Jorge S. Reis-Filho, and John H.J. Petrini.<\/em><\/p>\n

The study was supported by Susan G. Komen, the National Cancer Institute, the National Institutes of Health, the UNC Lineberger core grant, the Memorial Sloan Kettering Cancer Center core grant, and the University Cancer Research Fund. Individual researchers were supported by the Breast Cancer Research Foundation and the Ruth L. Kirchstein National Research Service Award Individual Postdoctoral Fellowship.<\/em><\/p>\n

Conflicts of interest: Gupta has ownership interests, including patents, in and is a consultant\/advisory board member for Naveris Inc. outside the scope of the present study.<\/em><\/p>\n

Reis-Filho<\/em>\u00a0reports personal\/consultancy fees from VolitionRx, Page.AI, Goldman Sachs, Grail, Ventana Medical Systems, Invicro, Roche Diagnostics, and Genentech, outside the scope of the present study.\u00a0<\/em>Petrini<\/em>\u00a0is a consultant for Ideaya Biosciences, Novus Biologicals, and Atropos Therapeutics, outside the scope of the present study.<\/em><\/p>\n

\u00a0<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

Researchers led by UNC BCBP’s Gaorav Gupta, MD, PhD, described the role of a mutation in the Mre11 gene in triple negative breast cancer and how a disruption of Mre11 function plays a significant role in the genomic instability of that cancer type. February 17, 2020 A hallmark of triple negative breast cancer, an aggressive … Read more<\/a><\/p>\n","protected":false},"author":86415,"featured_media":12011,"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":[10,308,298],"class_list":["post-12855","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-news","tag-news_faculty","tag-gaorav-p-gupta-news","tag-news_2020","odd"],"acf":[],"yoast_head":"\nResearchers implicate gene in DNA errors in aggressive 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\/researchers-implicate-gene-in-dna-errors-in-aggressive-breast-cancer\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Researchers implicate gene in DNA errors in aggressive breast cancer | Biochemistry and Biophysics\" \/>\n<meta property=\"og:description\" content=\"Researchers led by UNC BCBP’s Gaorav Gupta, MD, PhD, described the role of a mutation in the Mre11 gene in triple negative breast cancer and how a disruption of Mre11 function plays a significant role in the genomic instability of that cancer type. 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