Abstract P2-06-04: The power of next generation sequencing in the detection of breast and ovarian cancer susceptibility genes other than BRCA

Abstract

Background : Most cases of breast and ovarian cancer susceptibility remains unexplained. Testing multiple genes in one go with next generation sequencing is then an asset with the recent discovery of new genes involved in breast and ovarian cancer susceptibility. Methods : We studied 457 patients originated from Burgundy (France) fulfilling the criteria for BRCA1/2 testing using a next generation sequencing 25-gene panel including 17 genes of predisposition for breast and/or ovarian cancer (ATM, BARD1, BRCA 1/2, BRIP1, CHEK2, PALB2, RAD51C, TP53, PTEN, RAD50, MRE11, MLH1, MSH2, MSH6, PMS2, STK11). Results : A pathogenic BRCA1/2 mutation was found in 8% (n=37) of patients. Besides, we found 39 deleterious or probably deleterious mutations in 13 different genes. The most frequently mutated genes were CHEK2 (n=10 ; 2.1 %), ATM (n=9 ; 2 %), and PALB2 (n=4 ; 0.9%). One patient had deleterious mutations in both TP53 and PALB2, and another one had deleterious mutations in both BRCA2 and CHEK2. The mutation could explain the phenotype in the majority of cases, but a pathogenic mutation was found in a different predisposing gene in 7 patients, and could be considered as incidental findings with the currently published spectrum of cancer locations. Conclusion : Besides BRCA1/2 mutations, that remain the most frequent susceptibility genes for breast and ovarian cancer, gene panels remain a powerful tool for identifying the other less frequent susceptibility genes. The penetrance and spectrum of cancer associated to these other genes remain sometimes undefined, and further collaborative work is crucially needed to address this question. The possibility of double hits should led to careful genetic counseling. Citation Format: Eliade M, Skrypski J, Baurand A, Jacquot C, Bertolone G, Loustalot C, Coutant C, Guy F, Fumoleau P, Rivière J-B, Duffourd Y, Ghiringhelli F, Végran F, Boidot R, Lizard S, Faivre L. The power of next generation sequencing in the detection of breast and ovarian cancer susceptibility genes other than BRCA. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-06-04.