Establishment of a rapid mutation detection technique for screening of BRCA1 and BRCA2 genes

Abstract

People bearing germline mutations in either BRCAl or BRCA2 genes are more prone to breast cancer than other people. These two recently identified genes account for nearly 90% of the hereditary cancer cases. This number corresponds approximately to 100,000 women each year in Turkey. The individuals who carry these mutations are at high risk and characterizing these mutations will be helpful for providing them genetic counseling. This includes the estimation of risk for both the individual and his/her progeny. In addition, discovering the mutations is an important step in finding out the iunctions of these genes, which will give insights about how breast cancer is occurring In this study, we have established an easy and rapid mutation detection strategy; heteroduplex analysis, and tested its efficiency in 15 hereditary breast cancer patients. These patients have been screened for the entire exon 11 of BRCAl, which is 50% o f the entire coding region. In addition, half of the exon 11 of BRCA2, which is roughly one fourth of the coding region was examined in 10 patients. As yet, no mutation in the Turkish patients have been encountered These results exclude exon 11 of the BRCAl gene and part of exon 11 of the BRCA2 gene for nucleotide deletions and insertions as the cause of hereditary breast cancer in Turkey. In order to verily the efficiency of the technique, we have also screened four French hereditary breast cancer patients with previously characterized BRCAl mutations in exon 11, and confirmed the presence o f the mutations in the majority o f the cases With the technique, firmly established in our laboratory, we plan to analyze the remaining coding regions of the BRCAl and BRCA2 genes in our patient samples and in additional patients.