Characterization of BRCA1 and BRCA2 genetic variants in a cohort of Bahraini breast cancer patients using next-generation sequencing

Background: Breast cancer is the most common malignancy in women worldwide. About 5%-10% are due to hereditary predisposition. The contribution of BRCA1/2 mutations to familial breast cancer in Bahrain has not been explored. The objective of this study was to investigate the spectrum of BRCA1/2 genetic variants and estimate their frequencies in familial breast cancer. We also aim to test the efficiency of the next-generation sequencing (NGS) as a powerful tool for detecting genetic variation within BRCA1/2 genes.

Methods: Twenty-five unrelated female patients diagnosed with familial breast cancer were screened for BRCA1/2 variants. All targeted coding exons and exon-intron boundaries of BRCA1/2 genes were amplified with 167 pairs of primers by NGS.

Results: We have identified two deleterious BRCA1/2 variants in two patients, one in BRCA1 gene (c.4850C>A) and other in BRCA2 gene (c.67+2T>C). In addition to the deleterious variants, we identified 24 distinct missense variants of uncertain significance, 10 of them are seen to confer minor but cumulatively significant risk of breast cancer.

Conclusion: Our data suggest that BRCA1/2 variants may contribute to the pathogenesis of familial breast cancer in Bahrain. It also shows that NGS is useful tool for screening BRCA1/2 genetic variants of probands and unaffected relatives.