Among 1915 patients with ovarian cancer, almost 1 in 5 had inherited mutations in genes associated with risk of ovarian cancer. Furthermore, a total of 11 genes are now suspected of causing hereditary ovarian cancer, according to a report published in JAMA Oncology (doi:10.1001/jamaoncol.2015.5495).1

Although genetic mutations in the BRCA1 and BRCA2 genes are linked to a higher risk for ovarian, fallopian tube, or peritoneal cancer, this study sought to identify other inherited, or germline, mutations that increase the risk of these diseases. The study occurred through the efforts of the Gynecologic Oncology Group (GOG).

“Descriptions of the identity of these genes and their frequency was lacking in the medical literature,” explained Paul DiSilvestro, MD, head of research with the Program in Women’s Oncology at Women & Infants Hospital and professor of obstetrics and gynecology at The Warren Alpert Medical School of Brown University in Providence, Rhode Island, and coauthor of the study. “The goal of this research was to better define these issues.”

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The researchers examined germline (inherited) DNA through targeted capture and multiplex sequencing. The sequence data and the mutation frequencies revealed were compared with the National Heart, Lung and Blood Institute GO Exome Sequencing Project and the Exome Aggregation Consortium. Mutation status was compared with clinical characteristics and survival rates.

Approximately 18% of women with ovarian cancer were found to have mutations in genes associated with ovarian cancer risk, including genes beyond the BRCA1 and BRCA2 genes. Now 11 genes are suspected of being associated with ovarian cancer: BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH2, MLH1, PMS2, MSH6, PALB2, and BARD1.

“The results of this trial expanded our knowledge of the genes that we suspect cause hereditary ovarian cancer, bringing the total to 11,” DiSilvestro said.

“Genetic testing should now begin screening for these nine additional genetic mutations so women carrying the genes can make educated decisions about their health care future.”


1. Norquist BM, Harrell MI, Brady MF, et al. Inherited mutations in women with ovarian carcinoma [published online ahead of print December 30, 2015]. JAMA Oncol. doi:10.1001/jamaoncol.2015.5495.