Mutation screening of the BRCA1 gene in sporadic breast cancer in the Central of Iran

The purpose of the work was to study mutation screening of BRCA1 in Iranian patients with sporadic breast cancer. We carried out a mutational analysis of BRCA1 gene in 101 breast cancer patients from a population in Central of Iran. The comparison of DNA of paraffin-embedded breast cancer tissue from patients was studied, and breast tissue from 30 unrelated normal women without cancer was selected as controls. The entire BRCA1 coding sequence was amplified by PCR with primers especially designed for comprehensive mutation screening by single-strand conformation polymorphism (SSCP) analysis. The PCR products revealing abnormal SSCP migration pattern were sequenced. Then, in silico investigation was performed to identify the effects of new mutations on stability and function of BRCA 1.A total of ten nucleotide alterations were observed in the breast cancer tissue DNA. Six cases of single nucleotide changes in BRCA1 were detected in the study without records in the BIC database consisted four polymorphism in exon 11 (1543 Del G, 1597C > T, 2246 Del T, 2612C > G), one missense mutation in exon 7 (490C > T), and one deletion mutation in exon 10 (743 Del C). No nucleotide alterations were detected in the controls. In addition, the results of in silico analysis indicated that three mutations including 2612C > G, 1543 Del G and 743 Del C were not recorded in the especial database. Furthermore, the results of molecular docking studies confirmed that 2612C > G could change physicochemical properties of BRCA1. The findings of the present study suggest that screened mutations may have an important role on the incidence of breast cancer in women.