title: Somatic genetic alterations in BRCA2-associated and sporadic male breast cancer.
abstract: The genetic changes underlying the development and progression of male breast cancer are poorly understood. Germline BRCA2 mutations account for a significant part of male breast cancer, but the majority of patients 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 from each other and from sporadic breast cancer. In the present study, we performed a genome-wide survey by comparative genomic hybridization (CGH) of somatic genetic aberrations in 26 male breast cancers, including 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 were +1q (38%), +8q (33%), +17q (33%), -13q (29%), and -8p (24%). In tumors from BRCA2 mutation carriers, the five most common genetic changes 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 substantial hormonal differences between females and males, similar genetic changes are selected for during tumor progression. Furthermore, the presence of a highly penetrant germline BRCA2 mutation apparently leads to a characteristic somatic tumor progression pathway, again shared between affected male and female mutation carriers.
authors.affiliation: Laboratory of Cancer Genetics, Institute of Medical Technology, Tampere University Hospital and University of Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Tirkkonen
authors.forename: T
authors.initials: T
authors.lastname: Kainu
authors.forename: N
authors.initials: N
authors.lastname: Loman
authors.forename: O T
authors.initials: OT
authors.lastname: Jóhannsson
authors.forename: H
authors.initials: H
authors.lastname: Olsson
authors.forename: R B
authors.initials: RB
authors.lastname: Barkardóttir
authors.forename: O P
authors.initials: OP
authors.lastname: Kallioniemi
authors.forename: A
authors.initials: A
authors.lastname: Borg
mesh_terms: D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics*; D002869:Chromosome Aberrations; D005260:Female; D006580:Genetic Carrier Screening; D005819:Genetic Markers; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D005819:Genetic Markers; D009363:Neoplasm Proteins; D014157:Transcription Factors