BRCA1 and BRCA2 Germline Mutation Analysis in Hereditary Breast/Ovarian Cancer Families from the Aures Region (Eastern Algeria): First Report

Abstract : Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. In this study, we aimed to investigate the mutation spectrum of BRCA1 and BRCA2 genes in hereditary breast/ovarian cancer (HBOC) families from the Aures region (eastern Algeria). High risk breast/ovarian cancer families were selected from overall 1162 consecutive patients collected from cancer registry of anticancer center of Batna. Breast cancers were diagnosed between 2011 and 2015. Recurrent mutations on BRCA1 and BRCA2 previously found in Algerian patients were screened using PCR-direct sequencing in 113 HBOC families. In addition, for the first time in Algeria, HBOC patients were analyzed by NGS using a cancer panel of 30 hereditary cancer genes or BRCA1/2 genetic test. Six distinct deleterious mutations in BRCA1 and BRCA2 and a new VUS in PALB2 were detected in ten patients. Two distinct BRCA2 pathogenic variants c.1813dupA and c.8485C > T detected in two young female triple negative breast cancer (TNBC) patients, respectively, with a family history of male breast cancer, are reported here for the first time in Algerian population. Interestingly, we also detected a BRCA exon 15 deletion in two unrelated young female TNBC patients with strong family history of breast/ovarian cancer. Our study showed differences in the distribution of the mutation spectrum of BRCA genes between the Aures region and the north central region of Algeria. Our results will contribute in the implementation of genetic counseling and testing for patients and families at risk of hereditary breast and ovarian cancer.