Genes Contributing to Hereditary Ovarian Cancer in Women and BRCA1/2 Wildtype Families

Ovarian Cancer

ovarian cancer, BRCA1, BRCA2, BROCA

The investigators propose to test for non-BRCA1/2 mutations in new and existing families with hereditary ovarian cancer in order to better define penetrance and associated malignancies of rare ovarian cancer susceptibility genes. The hypothesis is at least one third of hereditary ovarian carcinoma families wildtype for BRCA1/2 can be solved using an updated version of BROCA (BROCA-HR) that targets 47 genes, including all known ovarian cancer genes and additional candidate genes in related pathways. The objective is to identify families with mutations in rare ovarian cancer susceptibility genes and test both affected and unaffected family members, thereby generating a rough estimate of penetrance for each mutated gene as well as identify new ovarian cancer susceptibility genes. The investigators also plan to enroll self identified African America women, who have been drastically under-represented in clinical cancer genetic testing programs and in OC susceptibility research.

There is more to hereditary ovarian cancer than the breast and ovarian cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2). Next generation sequencing techniques have made it possible to sequence multiple candidate ovarian carcinoma susceptibility genes simultaneously. The King Laboratory has developed a targeted capture and massively parallel sequencing test called BROCA to evaluate mutations in known or suspected breast and ovarian cancer genes. In a prospective series of 360 unselected women with ovarian carcinoma, the investigators found that nearly one fourth of women carried mutations in one of 13 genes, and mutations in genes other than BRCA1 and BRCA2 accounted for 26% of all inherited mutations. While BROCA and similar gene panels are already in clinical use, little is known about the relative risks of carrying these non-BRCA1/2 mutations, making it difficult to counsel unaffected family members and develop optimum prevention protocols.

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United States