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Somatic genetic alterations in BRCA2-associated and sporadic male breast cancer

✍ Scribed by Mika Tirkkonen; Tommi Kainu; Niklas Loman; Óskar T. Jóhannsson; Håkan Olsson; Rósa B. Barkardóttir; Olli-P. Kallioniemi; Åke Borg


Publisher
John Wiley and Sons
Year
1999
Tongue
English
Weight
254 KB
Volume
24
Category
Article
ISSN
1045-2257

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✦ Synopsis


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 ϩ1q (38%), ϩ8q (33%), ϩ17q (33%), -13q (29%), and -8p (24%). In tumors from BRCA2 mutation carriers, the five most common genetic changes were ϩ8q (100%), ϩ20q (100%), ϩ17q (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.


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