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Location of Mutation in BRCA2 Gene and Survival in Patients with Ovarian Cancer.
Labidi-Galy, S Intidhar; Olivier, Timothée; Rodrigues, Manuel; Ferraioli, Domenico; Derbel, Olfa; Bodmer, Alexandre; Petignat, Patrick; Rak, Beata; Chopin, Nicolas; Tredan, Olivier; Heudel, Pierre-Etienne; Stuckelberger, Sarah; Meeus, Pierre; Meraldi, Patrick; Viassolo, Valeria; Ayme, Aurélie; Chappuis, Pierre O; Stern, Marc-Henri; Houdayer, Claude; Stoppa-Lyonnet, Dominique; Buisson, Adrien; Golmard, Lisa; Bonadona, Valérie; Ray-Coquard, Isabelle.
Afiliación
  • Labidi-Galy SI; Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland. intidhar.labidi-galy@hcuge.ch.
  • Olivier T; Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
  • Rodrigues M; Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France.
  • Ferraioli D; Inserm U830, PSL Research University, Institut Curie, Paris, France.
  • Derbel O; Department of Surgery, Centre Léon Bérard, Lyon, France.
  • Bodmer A; Institut du Cancer Jean Mermoz, Lyon, France.
  • Petignat P; Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
  • Rak B; Department of Gynecology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
  • Chopin N; Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
  • Tredan O; Department of Surgery, Centre Léon Bérard, Lyon, France.
  • Heudel PE; Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
  • Stuckelberger S; Department of Medical Oncology, Centre Léon Bérard, Lyon, France.
  • Meeus P; Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
  • Meraldi P; Department of Surgery, Centre Léon Bérard, Lyon, France.
  • Viassolo V; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
  • Ayme A; Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
  • Chappuis PO; Department of Genetic, Laboratory and Pathology Medicine, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
  • Stern MH; Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
  • Houdayer C; Department of Genetic, Laboratory and Pathology Medicine, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
  • Stoppa-Lyonnet D; Inserm U830, PSL Research University, Institut Curie, Paris, France.
  • Buisson A; Division of Genetics, Pôle de Médecine diagnostique et théranostique, Institut Curie, Paris, France.
  • Golmard L; Inserm U830, PSL Research University, Institut Curie, Paris, France.
  • Bonadona V; Division of Genetics, Pôle de Médecine diagnostique et théranostique, Institut Curie, Paris, France.
  • Ray-Coquard I; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Clin Cancer Res ; 24(2): 326-333, 2018 01 15.
Article en En | MEDLINE | ID: mdl-29084914
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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Biomarcadores de Tumor / Proteína BRCA2 / Mutación Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Biomarcadores de Tumor / Proteína BRCA2 / Mutación Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Clin Cancer Res Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Estados Unidos