Abstract

In 2005, a molecular pathology group led by AM Chinnaiyan used a novel computational analysis of pre-existing microarray datasets and uncovered recurrent gene fusions involving the prostate-specific gene transmembrane protease, serine 2 (TMPRSS2) and members of the erythroblastosis virus E26 transforming sequence (ETS) family of transcription factors in prostate cancer (PCa). The most frequent partner in the fusion was the ERG gene located at locus 21q22.2. TMPRSS2-ERG fusions are identifiable by a variety of molecular platforms, including fluorescent in situ hybridization (FISH), RT-PCR, and quantitative real-time RT-PCR, in 40%-60% of the acinar PCa. Although the significance of the rearrangement in terms of patient outcome remains somewhat controversial, it is now clear that TMPRSS2-ERG fusion is an early and specific event in the oncogenesis of PCa, with potential utility as a biomarker for PCa screening and diagnosis. 1 Tomlins S.A. Rhodes D.R. Perner S. et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005; 310: 644-648 Crossref PubMed Scopus (3056) Google Scholar , 2 Morris D.S. Tomlins S.A. Montie J.E. et al. The discovery and application of gene fusions in prostate cancer. BJU Int. 2008; 102: 276-282 Crossref Scopus (40) Google Scholar Detection of TMPRSS2-ERG Fusion Gene Expression in Prostate Cancer Specimens by a Novel Assay Using Branched DNAUrologyVol. 74Issue 5PreviewTo develop a novel assay that uses branched DNA technology to measure TMPRSS2-ERG fusion, as genetic rearrangement of TMPRSS2 regulatory sequences and coding sequences of the ERG gene has been detected in nearly half of prostate cancers, but quantitative assays to detect such TMPRSS2-ERG gene fusion have been limited to real-time polymerase chain reaction (PCR) techniques that rely on reverse transcriptase-based amplification. Full-Text PDF ReplyUrologyVol. 74Issue 5PreviewThe editorial comment provides an important counterbalance to our report of a new method for detecting TMPRSS2-ERG gene rearrangement in prostate cancer. This gene rearrangement juxtaposes a prostate-specific promoter (TMPRSS2) with a transcription factor that is not normally expressed in the prostate (ERG) and leads to expression of high levels of ERG by prostate cells that normally would not express ERG. The ERG transcription factor, in turn, can lead to expression of a host of other genes that are not expressed in normal prostate epithelium. Full-Text PDF

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