Somatic mutation profiling among Pakistani females with breast cancer carrying alterations in various genes by whole exome sequencing

Breast cancer susceptibility genes like BRCA1 and BRCA2 have been extensively studied and found to be highly mutated. Additionally, other high penetrance genes associated with BC, such as P53, PTEN, and STK11, were considered. This study aimed to assess somatic mutations in Pakistani female breast cancer patients. Tumor samples were obtained from Jinnah Hospital Lahore, and whole-exome sequencing was conducted. The categorization of gene mutations revealed various types: 15.16 % synonymous single nucleotide variants, 14.19 % nonsynonymous, 1.81 % frameshift deletions, 1.95 % non-frameshift deletions, 1.25 % stopgain, and 0.14 % stop loss. Among 39 analyzed genes, prevalence of mutations varied. BRCA2 showed mutations in 83.33 % of cases, while ATM, BARD1, CDH12, CHEK2, MRE11, NBN, PMS2, PTEN, and RAD51C exhibited mutations in 50 % of cases. BARD1, MSH6, MUTYH, PALB2, and RAD50 had mutations in 66.67 % of cases, whereas MLH1, MSH2, and STK11 displayed frequencies of 33.33 %. PMS1 showed a mutation rate of 16.67 %. Gene mutations in early-onset Pakistani breast cancer patients, with BRCA2, BARD1, PALB2, and RAD50 being the most frequently mutated gene. The predominance of SNVs suggests major role for point mutations, while less frequent indels also contribute to tumorigenesis. Mutation patterns were similar to those observed in the Chinese population, indicating potential regional overlap. New somatic alterations in different genes among early-onset Pakistani BC patients were found, like Chinese population. BRCA2 and BRCA1 were most frequently mutated genes, with other genes showing mutations to lesser extent. Other genes may become frequently mutated in future, emphasizing importance of research.