Location of Mutation in Gene and Survival in Patients with Ovarian Cancer.

BRCA2 plays a central role in homologous recombination by loading RAD51 on DNA breaks. The objective of this study is to determine whether the location of mutations in the RAD51-binding domain (RAD51-BD; exon 11) of gene affects the clinical outcome of ovarian cancer patients. A study cohort of 353 women with ovarian cancer who underwent genetic germline testing for and genes was identified. Progression-free survival (PFS), platinum-free interval (PFI), and overall survival (OS) were analyzed. The Cancer Genome Atlas (TCGA) cohort of ovarian cancer ( = 316) was used as a validation cohort. In the study cohort, 78 patients were carriers of germline mutations of After adjustment for FIGO stage and macroscopic residual disease, carriers with truncating mutations in the RAD51-BD have significantly prolonged 5-year PFS [58%; adjusted HR, 0.36; 95% confidence interval (CI), 0.20-0.64; = 0.001] and prolonged PFI (29.7 vs. 15.5 months, = 0.011), compared with noncarriers. carriers with mutations located in other domains of the gene do not have prolonged 5-year PFS (28%, adjusted HR, 0.67; 95% CI, 0.42-1.07; = 0.094) or PFI (19 vs. 15.5 months, = 0.146). In the TCGA cohort, only carriers harboring germline or somatic mutations in the RAD51-BD have prolonged 5-year PFS (46%; adjusted HR, 0.30; 95% CI, 0.13-0.68; = 0.004) and 5-year OS (78%; adjusted HR, 0.09; 95% CI, 0.02-0.38; = 0.001). Among ovarian cancer patients, carriers with mutations located in the RAD51-BD (exon 11) have prolonged PFS, PFI, and OS. .