The landscape of candidate driver genes differs between male and female breast cancer

PLoS One. 2013 Oct 23;8(10):e78299. doi: 10.1371/journal.pone.0078299. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / physiopathology
  • Breast Neoplasms, Male / genetics*
  • Breast Neoplasms, Male / physiopathology
  • Carcinogenesis / genetics*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Computational Biology / methods
  • Female
  • Genes, Neoplasm / genetics*
  • Genetic Markers / genetics
  • Humans
  • Male
  • Middle Aged
  • Sweden
  • Thy-1 Antigens / genetics
  • Thy-1 Antigens / metabolism

Substances

  • Cell Cycle Proteins
  • Genetic Markers
  • SPAG5 protein, human
  • Thy-1 Antigens

Grants and funding

This study was supported by grants from the Swedish Cancer Society, the G Nilsson Cancer Foundation, the Mrs. B Kamprad Foundation, the King Gustaf V’s Jubilee Foundation, the Lund University Hospital Research Foundation and governmental funding of clinical research within the national health services (ALF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.