A Novel Subset of Human Tumors That Simultaneously Overexpress Multiple E2F-responsive Genes Found in Breast, Ovarian, and Prostate Cancers.
Reasoning that overexpression of multiple E2F-responsive genes might be a useful marker for RB1 dysfunction, we compiled a list of E2F-responsive genes from the literature and evaluated their expression in publicly available gene expression microarray data of patients with breast cancer, serous ovarian cancer, and prostate cancer. In breast cancer, a group of tumors was identified, each of which simultaneously overexpressed multiple E2F-responsive genes. Seventy percent of these genes were concerned with cell cycle progression, DNA repair, or mitosis. These E2F-responsive gene overexpressing (ERGO) tumors frequently exhibited additional evidence of Rb/E2F axis dysfunction, were mostly triple negative, and preferentially overexpressed multiple basal cytokeratins, suggesting that they overlapped substantially with the basal-like tumor subset. ERGO tumors were also identified in serous ovarian cancer and prostate cancer. In these cancer types, there was no evidence for a tumor subset comparable to the breast cancer basal-like subset. A core group of about 30 E2F-responsive genes were overexpressed in all three cancer types. Thus, it appears that disorders of the Rb/E2F axis can arise at multiple organ sites and produce tumors that simultaneously overexpress multiple E2F-responsive genes.
President and CEO, Intelligent Oncotherapeutics Incorporated, Pittsburgh, PA, USA.
Stanley E
SE
Shackney
Graduate student of Computational Biology, Lane Center for Computational Biology and Joint Carnegie Mellon/University of Pittsburgh Ph.D. Program in Computational Biology, Carnegie Mellon University, Pittsburgh, PA, USA.
Salim Akhter
SA
Chowdhury
Professor of Biological Sciences and Computational Biology, Department of Biological Sciences and Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, PA, USA.
Russell
R
Schwartz
E2F; Rb; basal-like; breast cancer; expression microarray; gene overexpression