Abstract 1451: BRCA1 and BRCA2 germline mutational spectrum in Algerian triple negative breast cancer (TNBC) patients
Authors: Cherbal Farid , Mehemmai Chiraz , Gaceb Hadjer , Mahfouf Hassen , Boualga Kada 
Published: June 2022

Abstract
Background: Breast cancer is currently the leading cause of cancer morbidity and mortality among Algerian women. To date, triple negative breast cancer (TNBC) shows substantial overlap with basal type cancer and it is associated with aggressive tumor behavior, poor prognosis and BRCA1 mutations. In the present study, we screened for the prevalence of BRCA1 and BRCA2 germline mutations in a cohort of 169 TNBC patients using PCR-Sanger sequencing and NGS with a cancer panel of 30 hereditary cancer genes or BRCA1/BRCA2 genetic test.
Materials and Methods: 169 TNBC patients and their relatives were referred trough several public hospitals from six years (2013-2019). BRCA1 germline mutation was screened using PCR-Sanger sequencing in 66 TNBC patients with strong family history of breast and ovarian cancer and 103 sporadic TNBC patients including all exons where a mutation was previously found in Algerian population (exons 2, 3, 4, 10, 17 and 19). BRCA2 germline mutation was screened using PCR-Sanger sequencing in 24 TNBC patients with strong family history of breast cancer including all exons where a mutation was previously found in Algerian patients (exons 10 and 22). In addition, nine (9) TNBC patients with strong family history of breast and ovarian cancer were analyzed by NGS using BRCA1 and BRCA2 test or a cancer panel of 30 hereditary genes (Colors genomics).
Results: The analysis of the genomic DNA samples of 169 TNBC patients revealed that 15 patients carried pathogenic germline variants in BRCA1 gene and three patients carried pathogenic variants in BRCA2 gene (10.65%). Eight distinct germline mutations in BRCA1 have been detected in this study: c.83_84delTG, c.181T&gt;G, c.798_799delTT, c.505C&gt;T, c.923_924delGC, c.2125_2126insA, c.5257A&gt;G and deletion of exon 15. Interestingly, the recurrent and specific mutation c.83_84delTG has been detected in 4 unrelated TNBC patients. The pathogenic variant c.2125_2126insA has been detected in three unrelated families and also in the first relatives of 2 patients. The rare likely pathogenic variant BRCA1 c.5257A&gt;G/p.Arg1753Gly has been detected in young female TNBC patient. The Del exon 15 in BRCA1 has been detected in two unrelated patients. Three distinct germline mutations in BRCA2 have been detected in three TNBC patients: c.1813dupA, c.7654dupA and c.8485C&gt;T. Interestingly, these three mutations are reported for the first time in Algerian population. The c.1813dupA and c.8485C&gt;T pathogenic variants have been detected in two young female TNBC patients with a family history of male breast cancer.
Conclusions: In the current study, we detected recurrent germline mutations in BRCA1 gene in early onset TNBC patients. BRCA2 pathogenic variants have also been detected in young female TNBC patients. TNBC immunophenotype should be considered as an additional criterion for genetic counselling and testing of BRCA genes in Algerian women with early onset breast cancer.
Citation Format: Farid Cherbal, Chiraz Mehemmai, Hadjer Gaceb, Hassen Mahfouf, Kada Boualga. BRCA1 and BRCA2 germline mutational spectrum in Algerian triple negative breast cancer (TNBC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1451.