Differential Sensitivity of Germline and Somatic BRCA Variants to PARP Inhibitor in High-Grade Serous Ovarian Cancer.

Autor: Vendrell JA; Laboratoire de Biologie des Tumeurs Solides, Département de Pathologie et Oncobiologie, CHU Montpellier, Université de Montpellier, 34295 Montpellier, France., Ban IO; Laboratoire de Biologie des Tumeurs Solides, Département de Pathologie et Oncobiologie, CHU Montpellier, Université de Montpellier, 34295 Montpellier, France., Solassol I; Unité de Recherche Translationnelle, Institut Régional du Cancer de Montpellier (ICM), 34090 Montpellier, France., Audran P; Département d'Anatomo-Pathologie, Institut Régional du Cancer de Montpellier (ICM), Université de Montpellier, 34090 Montpellier, France., Cabello-Aguilar S; Laboratoire de Biologie des Tumeurs Solides, Département de Pathologie et Oncobiologie, CHU Montpellier, Université de Montpellier, 34295 Montpellier, France.; Montpellier BioInformatics for Clinical Diagnosis (MOBIDIC), Molecular Medicine and Genomics Platform (PMMG), CHU Montpellier, 34295 Montpellier, France., Topart D; Oncologie Médicale, CHU Montpellier, Université de Montpellier, 34295 Montpellier, France., Lindet-Bourgeois C; Oncologie Médicale, CHU Montpellier, Université de Montpellier, 34295 Montpellier, France., Colombo PE; Département de Chirurgie Oncologique, Institut Régional du Cancer de Montpellier (ICM), 34090 Montpellier, France., Legouffe E; Oncologie Médicale, Institut de Cancérologie du Gard, 30900 Nîmes, France., D'Hondt V; Département d'Oncologie Médicale, Institut Régional du Cancer de Montpellier (ICM), Université de Montpellier, 34090 Montpellier, France., Fabbro M; Département d'Oncologie Médicale, Institut Régional du Cancer de Montpellier (ICM), Université de Montpellier, 34090 Montpellier, France., Solassol J; Laboratoire de Biologie des Tumeurs Solides, Département de Pathologie et Oncobiologie, CHU Montpellier, Université de Montpellier, 34295 Montpellier, France.; Montpellier Research Cancer Institute (IRCM), Institut National de la Santé et de la Recherche Médicale (INSERM) U1194, University of Montpellier, 34298 Montpellier, France.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Sep 16; Vol. 24 (18). Date of Electronic Publication: 2023 Sep 16.
DOI: 10.3390/ijms241814181
Abstrakt: Purpose: The introduction of PARP inhibitors (PARPis) as a treatment option for patients with high-grade serous ovarian cancer (HGSOC) modified the approach of BRCA testing worldwide. In this study, we aim to evaluate the impact of BRCA1 and BRCA2 variants on treatment response and survival outcomes in patients diagnosed in our institution.
Methods: A total of 805 HGSOC samples underwent BRCA1 and BRCA2 variant detection by using next-generation sequencing (NGS). Among them, a pathogenic alteration was detected in 104 specimens. Clinicopathological features and germline status were recovered, and alteration types were further characterized. The clinical significance of variant type in terms of response to chemotherapy and to PARPis as well as overall survival were evaluated using univariate analysis.
Results: In our cohort, 13.2% of the HGSOC samples harbored a pathogenic BRCA1 or BRCA2 variant, among which 58.7% were inherited. No difference was observed between germline and somatic variants in terms of the gene altered. Interestingly, patients with somatic variants only (no germline) demonstrated better outcomes under PARPi treatment compared to those with germline ones.
Conclusion: The determination of the inheritance or acquisition of BRCA1 and BRCA2 alterations could provide valuable information for improving management strategies and predicting the outcome of patients with HGSOC.
Databáze: MEDLINE
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