Increased prevalence of the founder BRCA1 c.5309G>T and recurrent BRCA2 c.1310_1313delAAGA mutations in breast cancer families from Northerstern region of Morocco: evidence of geographical specificity and high relevance for genetic counseling

Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 (BRCA1/2) confer high risks of breast and ovarian cancer. Because the contribution of BRCA1/2 germline mutations to BC in the Northeastern population of Morocco remains largely unknown, we conducted this first study to evaluate the prevalence and the phenotypic spectrum of two BRCA1/2 pathogenic mutations (the founder BRCA1 c.5309G>T and BRCA2 c.1310_1313delAAGA). This choice was also argued by the presence of an apparent specific geographical connection of these mutations and the Northeastern region of Morocco.

Our findings suggest that BRCA1 c.5309G>T and BRCA2 c.1310_1313delAAGA mutations may have a strong founder and/or recurrent effect on breast cancer among the Northeastern Moroccan population. There contribution to breast cancer incidence is certainly substantial in this subgroup. Therefore, we believe that BRCA1 c.5309G>T and BRCA2 c.1310_1313delAAGA mutations have to be included in the array of tests aimed at revealing cancer syndrome carriers among subjects of Moroccan origin.

Screening for the germline mutations c.5309G>T and BRCA2 c.1310_1313delAAGA was performed by sequencing on a total of 184 breast cancer (BC) patients originated from the Northeastern region of Morocco. The likelihood of identifying a BRCA mutation is calculated using the Eisinger scoring model. The clinical and pathologic features were compared between the BRCA-positive and BRCA-negative groups of patients. Difference in survival outcomes was compared between mutation carriers and non-carriers.

BRCA1 c.5309G>T and BRCA2 c.1310_1313delAAGA are responsible for a significant proportion of all BC cases (12.5%) and at least 20% of familial BC. The screening of BRCA1/2 genes by NGS sequencing confirmed that there are no additional mutations detected among positive patients. The clinicopathological features in positive patients were in accordance with typical characteristics of BRCA pathogenic mutations. The mean features in the carriers were the early onset of the disease, familial history, triple negative status (for BRCA1 c.5309G>T) and worse prognosis in terms of overall surviving. Our study indicates that the Eisinger scoring model could be recommended to identify patients for referral to BRCA1/2 oncogenetic counseling.