SOMATIC GENETIC ALTERATIONS IN BRCA2-ASSOCIATED AND SPORADIC MALE BREAST-CANCER

The genetic changes underlying the development and progression of male breast cancer are poorly understood. Germline BRCA2 mutations account : for a significant pan of male breast cancer, but the majority of pat ients lack a known inherited predisposition, We recently demonstrated that the progression of breast cancer in female carriers of a germline BRCA1 or BRCA2 mutation follows specific genetic pathways, distinct f rom each other and from sporadic breast cancer. In the present study, we performed a genome-wide survey by comparative genomic hybridization (CGH) of somatic generic aberrations in 26 male breast cancers, inclu ding five tumors from BRCA2 mutation carriers. BRCA2 tumors exhibited a significantly higher number of chromosomal aberrations than sporadic tumors. The most common alterations in sporadic male breast cancer we re +1q (38%), +8q (33%), + 17q (33%), -13q (29%), and -8p (24%). In tu mors from BRCA2 mutation carriers. the five most common genetic change s were +8q (100%), +20q (100%), +17q +80%), -13q (80%), and -6q (60%). The CGH results in these two groups of male breast cancers are almost identical to those identified in the corresponding sporadic and BRCA2 -associated female breast cancers, The results suggest that despite su bstantial hormonal differences between females and males, similar gene tic changes are selected For during tumor progression. Furthermore, th e presence of a highly penetrant germline BRCA2 mutation apparently le ads to a characteristic somatic tumor progression pathway, again share d between affected male and female mutation carriers. Genes Chromosome s Cancer 24:56-61, 1999. (C) 1999 Wiley-Liss, Inc