Location of Mutation in BRCA2 Gene and Survival in Patients with Ovarian Cancer

Article Article scientifique Article Location of Mutation in BRCA2 Gene and Survival in Patients with Ovarian Cancer eng 2018 author Labidi-Galy S Intidhar author Olivier Timothée 837722 author Rodrigues Manuel author Ferraioli Domenico author Derbel Olfa author Bodmer Alexandre 44155 author Petignat Patrick 586685 author Rak Beata Krystyna 845107 author Chopin Nicolas author Tredan Olivier author Heudel Pierre-Etienne author Stuckelberger Sarah author Meeus Pierre author Meraldi Patrick 0000-0001-9742-8756 108140 author Viassolo Valeria 847816 author Ayme Aurélie author Chappuis Pierre O author Stern Marc-Henri author Houdayer Claude author Stoppa-Lyonnet Dominique author Buisson Adrien author Golmard Lisa author Bonadona Valérie author Ray-Coquard Isabelle 326-333 10.1158/1078-0432.CCR-17-2136 29084914 1078-0432 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 affects the clinical outcome of ovarian cancer patients.Experimental Design: A study cohort of 353 women with ovarian cancer who underwent genetic germline testing for BRCA1 and BRCA2 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 (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 HR, 0.36; 95% confidence interval (CI), 0.20-0.64; P = 0.001] and prolonged PFI (29.7 vs. 15.5 months, P = 0.011), compared with noncarriers. 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 PFS, PFI, and OS. Clin Cancer Res; 24(2); 326-33. ©2017 AACR. Dewey 612 Dewey 618 134 Département de physiologie cellulaire et métabolisme 21C 58 Département de pédiatrie, gynécologie et obstétrique 223 false 579 Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) 922 590 Prévention du cancer du col utérin 933 Clinical Cancer Research 24 2 2be442d9-b666-4c01-bbae-c1a5ad44d1c2 Article (Published version) Restricted 326.full.pdf 729332 application/pdf restrictedAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique

Title	Published in	Access level	OA Policy	Year	Views	Downloads

Location of Mutation in BRCA2 Gene and Survival in Patients with Ovarian Cancer	Clinical Cancer Research			2018	525	1

Archive ouverte UNIGE

Rak, Beata Krystyna