AN INTERSTITIAL TANDEM DUPLICATION OF 9P23-24 COEXISTS WITH A MUTATION IN THE BRCA2 GENE IN THE GERM-LINE OF 3 BROTHERS WITH BREAST-CANCER

Germ-line mutations of the BRCA2 gene account for the majority of fami lies with both male and female breast cancer, However, among independe ntly ascertained families with the same mutation, cases of male breast cancer often appear to cluster in a single family or in a particular branch of one family, This suggests that the risk of male breast cance r conferred by BRCA2 mutations may be modified by other genetic or env ironmental factors, We report a family in which three brothers with br east cancer carry in their germ line two genetic abnormalities: an ins ertion A at nucleotide 2041 in exon 10 of BRCA2, which leads to premat ure termination of the encoded protein at codon 615, and a tandem inte rstitial duplication involving chromosome bands 9p23-24, We propose th at the coexistence of this rare chromosomal abnormality with BRCA2 mut ation may be augmenting the risk of male breast cancer conferred by th e BRCA2 mutation.