Abstract 2553: Prevalence of BRCA1 germline mutations in Algerian population: implications for genetic testing and counseling

Abstract Background: Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women.In this study, we estimated the prevalence of BRCA1 germline mutations in 192 patients with hereditary breast and/or ovarian cancer and sporadic triple-negative breast cancer, respectively. Materials and Methods: 192 Patients and their families were referred through several public hospitals and private medical clinics which provide oncology services throughout Algeria. Patients were selected for family history of breast and/or ovarian cancer. In addition, in the present study, all women (age under 50 years) with triple-negative breast cancer (TNBC) were considered eligible. BRCA1 was screened by PCR-direct sequencing in all patients including all exons where a mutation was previously found in Algerian population (exons 2, 3, 5 and 11). Results: The analysis of DNA samples of 192 individuals revealed that 11 patients carried pathologic germline mutations in BRCA1 gene (5.7%).Five distinct pathogenic mutations: c.19_47del, c.83_84delTG, c.181T>G, c.798_799delTT and c.2125_2126insA were indentified. Interestingly, the BRCA1 mutation c.83_84delTG detected in previous studies in two unrelated Algerian breast cancer families has been identified in this study in 4 patients with a frequency of 2% (4/192): 3 TNBC patients and one patient with a bilateral ovarian cancer, respectively. The four patients had a strong hereditary breast and/ or ovarian cancer history. The c.181T>G/p.Cys61Gly mutation has been detected here in two young breast cancer patients, a bilateral breast cancer patient with a family history of breast cancer and a young TNBC patient (diagnosed at age 36 years), respectively. To date, the Cys61Gly pathogenic variant is one of the most frequent founder mutation identified in Central European populations, has been previously reported for the first time in two Algerian and Moroccan families. The BRCA1 mutation c.798_799delTT was identified here in a young TNBC patient with a family history of breast cancer. Interestingly, this mutation has been previously detected in several unrelated families from Algeria, Tunisia, Morocco and Italy, respectively. As Mediterranean countries share a common history and migration flow history, BRCA1 mutation c.798_799delTT could be a Mediterranean founder mutation. The BRCA1 mutation c.2125_2126insA has been detected here for the first time in three young TNBC patients with a family history of breast cancer and prostate cancer. Conclusions: The accumulating knowledge about the prevalence and nature of BRCA1 mutations in Algerian population and the identification of specific mutations will contribute in the future to the implementation of genetic testing and counseling for families at risk. Based on our currents results, we recommend using the TNBC immunophenotype as criterion to screen for BRCA1 germline mutations in patients with early onset breast cancer. Citation Format: Farid Cherbal, Hadjer Gaceb, Chiraz Mehemmai, Rabah Bakour, Kamelia Yatta, Ikram Boukoufa, Hassen Mahfouf, Kada Boualga. Prevalence of BRCA1 germline mutations in Algerian population: implications for genetic testing and counseling. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2553.