Germline and Somatic Variants Analyzed in Ovarian Cancer

Genetic studies of inherited predisposition to ovarian cancer have tended to focus on women with a known family history of the disease.

For ovarian cancer patients with no known family history of the disease it has been found that one fifth of them had inherited alterations in genes known to be linked to ovarian and breast cancer.


Scientists at Washington University School of Medicine (St. Louis, MO, USA) working with colleagues from other institutes, studied 429 women with sporadic ovarian cancer who did not have a known family history of either ovarian or breast cancer or rare cancer syndromes, all of which are known to increase the risk of developing ovarian tumors. They analyzed DNA from each woman's tumor tissue and compared it with DNA from her skin. From this comparison, they could identify the acquired mutations in each tumor. They also compared the patients' skin DNA with that of 557 women without ovarian cancer to identify inherited mutations.

In total, the team found 222 inherited mutations that increase the risk for ovarian cancer. Some were already known about, for instance breast cancer 1, early onset (BRCA1) and BRCA2, while others have never been linked to ovarian cancer. They identified 3,635 high confidence, rare truncation, and 22,953 missense variants with predicted functional impact. They found germline truncation variants and large deletions across Fanconi pathway genes in 20% of cases. Enrichment of rare truncations was shown in BRCA1, BRCA2, and the gene Partner and Localizer of BRCA2 (PALB2). Evidence for loss of heterozygosity was found in 100% and 76% of cases with germline BRCA1 and BRCA2 truncations, respectively.

Li Dang, PhD, the senior author of the study, said, “Using advanced genomic analysis, we found that 20% of women with ovarian cancer had inherited mutations in a gene pathway known to be important in inherited breast and ovarian cancer. This number is pretty high and we need to find better ways to screen women for ovarian cancer, even if they don't have family histories of the disease.” The study was published on January 22, 2014, in the journal Nature Communications.

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