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Title

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

Authors
Labidi-Galy, S Intidhar
Rodrigues, Manuel
Ferraioli, Domenico
Derbel, Olfa
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Published in Clinical cancer research. 2018, vol. 24, no. 2, p. 326-333
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 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.
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PMID: 29084914
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Research groups Groupe Meraldi Patrick (physiologie cellulaire et métabolisme) (922)
Prévention du cancer du col utérin (933)
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LABIDI-GALY, S Intidhar et al. Location of Mutation in BRCA2 Gene and Survival in Patients with Ovarian Cancer. In: Clinical Cancer Research, 2018, vol. 24, n° 2, p. 326-333. doi: 10.1158/1078-0432.CCR-17-2136 https://archive-ouverte.unige.ch/unige:107105

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Deposited on : 2018-08-16

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