Molecular and pathological characterization of inherited breast cancer

The two major breast cancer susceptibility genes, BRCA1 and BRCA2, account for the majority of familial breast-ovarian cancer, but only a modest Propo rtion of breast cancer families without ovarian or male breast cancer Searc h for additional breast cancer genes with traditional linkage analysis has so far been unsuccessful, probably due to genetic heterogeneity. Pooling of families of different ethnical, cultural, and geographical origin proved t o be a useful approach when identifying BRGA1 and BRCA2, but for genes muta ted only in specific populations it is important not to introduce locus het erogeneity by Pooling. Genetic heterogeneity can possibly be circumvented b y using objective means, such as tumour histopathology or gene expression p rofiling, for subclassification of families prior to linkage analysis. Also , additional breast cancer genes can be identified by further characterizat ion of the function of BRCA1 and BRCA2 and their interacting proteins.