Investigation of Trinucleotide Repeat Expansion in Familial Breast Cancer

摘要

Our approach is based on the hypothesis that trinucleotide repeat expansion occurs in breast cancer. Our objective is to identify putative breast cancer predisposition gene(s) which are associated with expansions of trinucleotide repeats. In this project we have developed a Rapid Expansion Detection method which can be used very efficiently in the detection of repeat expansions using small amount of genomic DNA. In the analysis of population- based breast cancer cases (212) and controls (196), we have shown the allelic distribution of CAG repeats. The distribution of smaller repeats (40-96 repeats) did not vary greatly in cases and controls. However, we have shown that a fraction (2.3%) of breast cancer cases carried expanded CAG repeats (144 and more). Further investigation on the transmission of these CAG repeat expansions suggested a paternal transmission in 2 of the cases. These repeats may be associated with and affect the function of breast cancer predisposition genes. These genes will be identified by cloning. Our approach has the potential to allow the rapid identification of novel breast cancer predisposition genes which will provide obvious benefits for families with breast cancer, as well as the potential for insights into the pathobiology of this devastating disease.