Location of mutation in BRCA2 gene and survival in patients with ovarian cancer. - PubMed - NCBI
Clin Cancer Res. 2017 Oct 30. pii: clincanres.2136.2017. doi: 10.1158/1078-0432.CCR-17-2136. [Epub ahead of print]
Location of mutation in BRCA2 gene and survival in patients with ovarian cancer.
Labidi-Galy SI1,
Olivier T2,
Rodrigues M3,
Ferraioli D4,
Bodmer A5,
Petignat P6,
Rak B2,
Chopin N7,
Tredan O8,
Heudel PE9,
Stuckelberger SJ2,
Meeus P10,
Meraldi P11,
Viassolo V2,
Ayme A12,
Chappuis PO13,
Stern MH14,
Houdayer C15,
Stoppa-Lyonnet D16,
Buisson A17,
Golmard L18,
Bonadona V19,
Ray-Coquard I20.
Abstract
PURPOSE:
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 BRCA2 gene impacts the clinical outcome of OC patients. EXPERIMENTAL DESIGN:
A study cohort of 353 women with OC who underwent genetic germline testing for BRCA1 and BRCA2 genes were identified. Progression-free survival (PFS), platinum-free interval (PFI) and overall survival (OS) were analyzed. The Cancer Genome Atlas (TCGA) cohort of OC (n=316) was used as a validation cohort. RESULTS:
In the study cohort, 78 patients were carriers of germline mutations of BRCA2. After adjustment for FIGO stage and macroscopic residual disease, BRCA2 carriers with truncating mutations in the RAD51-BD have significantly prolonged 5-year PFS (58%; adjusted Hazard ratio [HR], 0.36; 95% CI, 0.20-0.64; p=0.001) and prolonged PFI (29.7 vs 15.5 months, p=0.011), compared to non-carriers. BRCA2 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; p=0.094) or PFI (19 vs 15.5 months, p=0.146). In the TCGA cohort, only BRCA2 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; p=0.004) and 5-year OS (78%; adjusted HR, 0.09; 95% CI, 0.02-0.38; p=0.001). CONCLUSIONS:
Among ovarian cancer patients, BRCA2 carriers with mutations located in the RAD51-BD (exon 11) have prolonged progression-free survival, platinum-free interval and overall survival. Copyright ©2017, American Association for Cancer Research.
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