Characterization of BRCA2 Mutations in a Series of Functional Assays

摘要

The BRCA2 breast and ovarian cancer predisposition gene was identified in 1995. Mutations in the gene account for approximately 20% of all hereditary breast cancer and perhaps 2% of all breast cancer cases. Many individuals undergo expensive clinical testing for mutations in the BRCA2 gene in order to provide information to their family members about risk of breast cancer. The majority of mutations identified during clinical testing result in truncation of the protein, while approximately 20% are missense mutations. The affect of these missense mutations on BRCA2 function is not known. Thus, these mutations are termed unclassified variants and women carrying these mutations are informed that their results are inconclusive. To improve upon this situation we have proposed to develop a series of functional assays that can be used to determine if particular missense mutations disrupt BRCA2 function and are disease associated or not.