Low BRCA1 and BRCA2 Germline Mutation Rates in a French-Canadian Population with a Diagnosis of Epithelial Tubo-Ovarian Carcinoma.

Autor:	Bernard J; Gynecologic Division, Hopital Couple Enfant, CHU Grenoble Alpes, Grenoble, France. Electronic address: JBernard7@chu-grenoble.fr., Mehros W; Princess Nourah Oncology Center, King Abdul-Aziz Medical City, Jeddah, Saudi Arabia., Gregoire J; Gynecologic Oncology Division, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec, Laval University, Quebec, QC., Douville P; Division of Medical Biochemistry, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec, Laval University, Quebec, QC., Renaud MC; Gynecologic Oncology Division, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec, Laval University, Quebec, QC., Sebastianelli A; Gynecologic Oncology Division, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec, Laval University, Quebec, QC., Langlais EL; Gynecologic Oncology Division, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec, Laval University, Quebec, QC., Plante M; Gynecologic Oncology Division, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec, Laval University, Quebec, QC.
Jazyk:	angličtina
Zdroj:	Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC [J Obstet Gynaecol Can] 2022 Oct; Vol. 44 (10), pp. 1047-1053. Date of Electronic Publication: 2022 Jun 30.
DOI:	10.1016/j.jogc.2022.06.005
Abstrakt:	Objective: Universal genetic testing has become increasingly important in the management of epithelial tubo-ovarian and peritoneal carcinoma. Worldwide, reported incidences of deleterious BRCA mutations vary between 12% and 15%. We sought to evaluate the incidence in our population, given its specific genetic background (French-Canadian ancestry). Method: Mainstream genetic testing was implemented in our service in May 2017 and offered to all patients with epithelial tubo-ovarian or peritoneal carcinomas, except mucinous and borderline tumours. Data were prospectively collected in a database and retrospectively analyzed. Results: We tested 222 patients in our centre, of whom 183 (82.4%) had high-grade serous carcinoma (HGSC). Overall, 139 patients had no identified mutation (62.6%). Deleterious BRCA1 and BRCA2 mutations were found in 12 patients (5.4%): 6 had BRCA1, and 6 BRCA2 mutations; 11 of these patients had HGSC. Other non-BRCA mutations (ATM, RAD51C, RAD51D, BRIP1, CDH1, MRE11, MSH6, MUTYH, PALB2, and PMS2) were observed in an additional 20 patients (9.0%), of whom 18 had HGSC. A total of 63 different variants of unknown significance (VUS) were found, of which 4 were in the BRCA1 and BRCA2 genes. Deleterious mutations were not identified in clear cell carcinomas, and only 1 was found in low-grade serous carcinoma. Conclusion: In our French-Canadian population, the incidence of deleterious germline BRCA mutations was surprisingly low at 5.4%-less than half that reported in the literature. This may affect patient response to poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) therapy. Mainstream genetic testing was successfully implemented in our service and facilitated access to genetic testing in our patient population. (Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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