Genome Instability in Mammary Cells of Pathogenic BRCA1/2 Mutation Carriers

BRCA1 or BRCA2 gene increase the risk of breast and ovarian cancer by elevating mutation rate in mammary cells. Here we show, using a single-cell whole genome sequencing approach, that mammary luminal epithelial cells isolated from tissues obtained from preventive mastectomy surgeries in women with a pathogenic BRCA1/2 germline mutation, exhibit a statistically significant, increased mutation frequency as compared to age-matched controls without genetic risk of breast cancer.]]>
Tissue samples included in the control group were obtained from women (mean age 40 SD+/-7.9) undergoing reduction mammoplasty for cosmetic reasons who reported no previous family history of breast cancer. The high breast cancer risk group included patients diagnosed with germline pathogenic mutations in BRCA1 or BRCA2 (mean age 41.1 SD+/-2.89); five tissues from the high risk group were collected from cancer-free female patients undergoing prophylactic tumor preventive mastectomy, three samples were non-tumor mammary tissue samples collected from patients diagnosed with early onset breast cancer.]]>