Prevalence of Novel and Recurrent Pathogenic Variants in Brca Genes in a Cohort of Iranian Hereditary Breast Cancer Patients Publisher



Sarmadi A ; Haghjooy Javanmard S ; Zeinalian M ; Hosseinzadeh M ; Tabatabaiefar MA
Source: Advanced Biomedical Research Published:2025

Abstract

Background: The incidence of breast cancer (BC) is increasing in Iranian women, especially in those with a positive family history of any type of cancer. Being a carrier of pathogenic variants in BRCA1/2 genes, significantly raises the risk of developing BC, mostly at young ages. Materials and Methods: We sequenced the entire coding regions of BRCA1/2 genes using next generation sequencing (NGS) in 50 selected patients with HBC criteria for genetic testing from a cohort of about 700 newly diagnosed BC patients. In the patient with novel pathogenic variant, bioinformatics and co-segregation study were performed, and American College of Medical Genetics and Genomics (ACMG) guidelines were used for the variant’s interpretation. Results: Among the 50 patients, pathogenic variants were found in 16 patients (12 in the BRCA1 and 4 in the BRCA2 gene) that were mainly frameshift index (50%). We identified a novel pathogenic variants (p.Cyc27Valfs*4) in BRCA1 and four which were not previously reported in Iranian BC patients. Interestingly, out of 12 pathogenic variants in the BRCA1 gene, three unrelated families had the same variant (p.Arg1203Term) which could be added as a recurrent variant in the Iranian population. Notably, the frequency of triple-negative breast cancer (TNBC) patients harboring BRCA1/2 mutations was significant (62.5%). Conclusions: Young age at onset and having a positive family history of cancer are among the most important criteria to perform genetic testing. Identification of the carriers of pathogenic variants in high-risk families and also recurrent variants in the population will contribute to prevent of HBC. © 2025 Advanced Biomedical Research.