Genetic Alterations in Familiar Breast Cancer: Mapping and Cloning Genes Otherthan BRCAl

摘要

The purpose of this project is to identify genes other than BRCA1 responsible forinherited predisposition to breast cancer, to identify critical mutations, to evaluate the frequency of inherited mutations in these genes among breast cancer patients from the general population, and to determine the role of somatic mutations in these genes in malignant breast tumors. The patient materials are kindreds with at least four cases of breast cancer, in whom disease is not linked to BRCA1. Twenty-one families have been sampled, lymphocyte lines established, and linkage evaluated at multiple chromosomal locales. Linkage analysis of these kindreds reveals convincing linkage to BRCA2 in three families and to the estrogen receptor in three other families. Five other candidate chromosomal regions have been screened as well. Probands from 139 other high-risk kindreds have been contacted. Of these families, 21 will be informative for linkage. Sampling of these 21 extended families is in progress. This will bring the cohort to 42 families in all.