Introduction and Objectives
Gene rearrangements can be an initial event in oncogenesis. Whereas prostate cancer (PrCa) specific TMPRSS2–ERG fusions are frequent genomic alterations, fewer TMPRSS2 fusions with other ETS transcription factors have been described. Cancer Outlier Profile Analysis (COPA) led to the identification of gene fusions in PrCa. Our recent study aims to use COPA analysis on the new Affymetrix exon 1.0 arrays to assess the prevalence of outliers in PrCa patients. We validated the technology using the ERG exon specific gene expression data.
Material and Methods
Based on the pathology findings of 70 radical prostatectomy specimens four groups of patients were identified: 1) low grade (LG-PrCa; n = 20), 2) high grade (HG-PrCa; n = 22) 3) castration resistant (CR-PrCa; n = 21) and 4) metastatic (Met-PrCa; n = 7). Following RNA isolation gene profiling was performed using a microarray technique (GeneChip, Affymetrix). We did bioinformatic analysis, including COPA on the standard gene set (23,000 genes).
250 outliers genes were identified on a microarray analysis. ETS transcription factors family genes: ERG, ETV1, ETV4 and ETV5 were selected for further experiments. ERG, ETV1, ETV4 and ETV5 were overexpressed in 39 (55%), 4 (5.7%), 2 (2.8%) and 2 (2.8%) of tumors, respectively. Further, in all tumors overexpressing ERG, TMPRSS2–ERG fusions were identified using an independent test. The overexpression of ETV1 and ETV5 was only observed in all cases of aggressive PrCa.
We confirmed in this COPA analysis of expression data from 70 prostate cancers the frequent overexpression of ETS oncogenes. Except from the common TMPRSS2–ERG fusions, we haven’t been able so far to identify new 5′ fusions partners. Additionally, we were able to show that ETV1 and ETV5 were overexpressed in patients with aggressive PrCa. Therefore, exon 1.0 ST arrays can be used to lead the way in the discovery of gene fusions.
© 2009 European Association of Urology. Published by Elsevier Inc. All rights reserved.