Identification of Nucleotide Changes of Two Known Causative Genes (BRCA۲ and STK۱۱) of Hereditary Breast Cancer in an Iranian Family using Exome Sequencing

Objective: Since the identification of the two highly penetrant dominantly inherited genes, BRCA۱/۲, in the ۱۹۹۰s, a number of other genes have been identified which account for approximately ۲۵% of the genetic basis for hereditary breast cancer. At least ۷۵% are unidentified. The goal of this study is to investigate the presence or absence of a recessive pattern of inheritance in this heterogeneous disease whose possibility has been previously discussed by researchers. Methods: In this study we used exome sequencing as the most recent approach for identification of the genetic basis of any disease. The results of exome sequencing were confirmed by Sanger sequencing. Results: Although we did not find any homozygous mutation in this family, however a heterozygous ۴bp deletion that led to a frame shift mutation was identified in exon ۱۱ of the BRCA۲ gene. Also identified was a heterozygous single nucleotide polymorphism in exon ۹ of the STK۱۱ gene. Conclusion:  The rs۸۰۳۵۹۳۵۲ variation identified in this family is one of the frequent pathogenic mutations in the BRCA۲ gene that has been reported in the BIC database. This variation has been previously observed in other ethnic populations such as Caucasians, Hispanics and the Chinese. In this study, for the first time, we report this mutation in Iranian population and its segregation in hereditary breast cancer.

کلیدواژه ها:

BRCA۲ ، rs۸۰۳۵۹۳۵۲ ، STK۱۱ ، Hereditary breast cancer ، Exome sequencing ، BRCA۲ ، rs۸۰۳۵۹۳۵۲ ، STK۱۱ ، سرطان پستان ارثی ، توالییابی اگزوم