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ETS-Related Gene (ERG), A Frequent Proto-Oncogene Expression and Fusion In Prostate Cancer With Potentials In Diagnosis and Prognosis
Gyorgy Petrovics
CPDR, Rockville, MD
Introduction: Prevalent alterations of proto-oncogenes in primary prostate cancer (CaP) are not well defined. Our evaluations of epithelial cell transcriptome of benign and malignant glands of CaP patients have revealed ETS-related gene (ERG) as one of the most frequent proto-oncogene overexpression in CaP.
Methods: Matched benign and malignant epithelial cells were obtained by laser capture micro-dissection (LCM) of radical prostatectomy (RP) specimens (N= 80 specimens; 40 CaP patients). RNA specimens from these cells were used for global gene expression profiling (Affymetrix GeneChip HG U133Plus). Quantitative expression analyses of ERG and two other genes commonly overexpressed in CaP cells (DD3 and AMACR) were performed by real time RT-PCR (TaqMan). Recently described TMPRSS2-ERG fusion break points were analyzed by RT-PCR.
Results: Striking overexpression of ERG was revealed in tumor cells in comparison to matched benign epithelial cells both by GeneChip analysis (N=40, 66%), and by TaqMan QRT-PCR (N=140, 74.30%) of CaP patients. Combined analysis of ERG, AMACR and DD3 revealed overexpression of at least one of these three genes in all CaP patients analyzed (N=70). Intriguingly, decreased ERG expression in tumor cells showed association with PSA recurrence after RP (p = 0.0006). The frequency of TMPRSS2-ERG gene fusion was evaluated in our patient cohort.
Conclusions: Our study underscores both diagnostic and prognostic features of ERG expression and TMPRSS2-ERG gene fusion in CaP. ERG overexpression is predominant in CaP patients with well differentiated prostate tumor. Decreased ERG expression associates with disease free survival after RP and with pathologic stage of the tumor.
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