title: The landscape of candidate driver genes differs between male and female breast cancer.
abstract: The rapidly growing collection of diverse genome-scale data from multiple tumor types sheds light on various aspects of the underlying tumor biology. With the objective to identify genes of importance for breast tumorigenesis in men and to enable comparisons with genes important for breast cancer development in women, we applied the computational framework COpy Number and EXpression In Cancer (CONEXIC) to detect candidate driver genes among all altered passenger genes. Unique to this approach is that each driver gene is associated with several gene modules that are believed to be altered by the driver. Thirty candidate drivers were found in the male breast cancers and 67 in the female breast cancers. We identified many known drivers of breast cancer and other types of cancer, in the female dataset (e.g. GATA3, CCNE1, GRB7, CDK4). In contrast, only three known cancer genes were found among male breast cancers; MAP2K4, LHP, and ZNF217. Many of the candidate drivers identified are known to be involved in processes associated with tumorigenesis, including proliferation, invasion and differentiation. One of the modules identified in male breast cancer was regulated by THY1, a gene involved in invasion and related to epithelial-mesenchymal transition. Furthermore, men with THY1 positive breast cancers had significantly inferior survival. THY1 may thus be a promising novel prognostic marker for male breast cancer. Another module identified among male breast cancers, regulated by SPAG5, was closely associated with proliferation. Our data indicate that male and female breast cancers display highly different landscapes of candidate driver genes, as only a few genes were found in common between the two. Consequently, the pathobiology of male breast cancer may differ from that of female breast cancer and can be associated with differences in prognosis; men diagnosed with breast cancer may consequently require different management and treatment strategies than women.
authors.affiliation: Division of Oncology, Department of Clinical Sciences, Lund and CREATE Health Strategic Center for Translational Cancer Research, Lund University, Lund, Sweden.
authors.forename: Ida
authors.initials: I
authors.lastname: Johansson
authors.forename: Markus
authors.initials: M
authors.lastname: Ringnér
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hedenfalk
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology; D018567:Breast Neoplasms, Male / Q000235:genetics* / Q000503:physiopathology; D063646:Carcinogenesis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D005260:Female; D052138:Genes, Neoplasm / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D013548:Sweden; D018800:Thy-1 Antigens / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D005819:Genetic Markers; C486663:SPAG5 protein, human; D018800:Thy-1 Antigens