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Introduction and Objectives: Our laboratory has been focusing on the discovery, biology and translational utility of the genes frequently altered in human prostate cancer (CaP) using global gene expression and genome scanning technologies. We report here the discovery of ETS-related gene (ERG) overexpression as one of the most frequent proto-oncogene alterations in CaP cells. Materials and Methods: Matched benign and malignant epithelial cells were obtained from radical prostatectomy specimens by laser capture micro-dissection (LCM). RNA specimens from these cells were analyzed for global gene expression using Affymetrix U133a GeneChips and Microarray Data Analysis software (NHGRI, NIH). Quantitative expression analyses of ERG and two other genes commonly overexpressed in CaP cells (DD3 and AMACR) were performed by real time/Taqman PCR and a correlation with clinico-pathologic features was evaluated. Results: Striking overexpression of ERG was revealed in prostate tumor cells in comparison to matched benign epithelial cells by GeneChip analysis in 78% of CaP patients (N=36 specimens; 18 CaP patients), as well as by TaqMan QRT-PCR analysis in 72% of CaP patients (N=164 specimens; 82 CaP patients). Combined analysis of ERG, AMACR and DD3 showed overexpression of at least one of these genes in prostate tumor cells of virtually all (98%) CaP patients (N=55). Intriguingly, increased expression of ERG1 was associated with better prognosis of CaP. Conclusions: Novel observations of frequent ERG overexpression in CaP cells are highly significant as transcription factors encoded by the ETS family of genes are central in integrating signals that regulate cell growth and differentiation, stress responses and tumorigenesis. This study underscores both diagnostic and prognostic features of ERG1 expression in prostate cancer.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]