Association of somatic mutations in BRCA2 BRC domain with chemotherapy sensitivity and survival in high grade serous ovarian cancer

Background: Mutations at sites crucial for the interaction between RAD51 and BRC domains impair the ability of BRCA2 homologous recombination. We aimed to clarify whether BRCA2 BRC domain-associated mutation correlates with sensibility of platinum-based chemotherapy and survival in high-grade serous ovarian cancer (HGSOC). Methods: We identified BRCA2 BRC domain mutations by sequencing PCR-amplified amplicons of genomic DNA isolated from tumor tissues and peripheral blood leukocytes (PBL)in 113 patients with advanced EOC, and assessed platinum-free interval (PFI), progression-free survival (PFS) and overall survival (OS). Results: 21.23% (24 of 113) cases with somatic missense mutation but not germline mutation were identified. Among 24 cases with mutation, 33.3% (8 of 24) cases with nonsense mutation (C-terminal truncation) significantly prolonged median PFI (37 vs 8 months,P = 0.000), PFS (43 vs 14 months, p = 0.000) and 05 (56 vs 31 months, P = 0.002); 66.7% (16 of 24) cases with missense mutation also prolonged median PFI (15 vs 8 months, P = 0.044), PFS (21 vs 14 months, P = 0.049) and 05 (38 vs 31 months, P = 0.037), compared to those without any mutation. Conclusions: Somatic mutations in BRCA2 BRC domain confer a higher sensitivity to platinum-based therapy and are associated with a favourable survival in HGSOC.

Automated summary

Somatic mutations in the BRCA2 BRC domain are associated with increased sensitivity to platinum-based therapy and improved survival outcomes in high-grade serous ovarian cancer.