Whole-transcriptome Analysis Reveals Established and Novel Associations with TMPRSS2:ERG Fusion in Prostate Cancer

Background/Aim: Shortcomings of current methods of prostate cancer detection call for improved biomarkers. The transmembrane protease, serine 2:ets-related gene (TMPRSS2:ERG) gene fusion leads to the overexpression of ERG, an E-twenty six (ETS) family transcription factor, and is the most prevalent genetic lesion in prostate cancer, but its clinical utility remains unclear. Materials and Methods: Two radical prostatectomy samples were analysed by next-generation whole-transcriptome sequencing. The chosen samples differed infusion gene status, as previously determined by reverse transcription polymerase chain reaction (RT-PCR). Results: Next-generation sequencing identified the involvement of novel and previously reported prostate cancer-related transcripts, the WNT signalling pathway, evasion of p53-mediated anti-proliferation and several ETS-regulated pathways in the prostate cancer cases examined. Overexpression of Rho GDP-dissociation inhibitor (RhoGDIB), a gene associated with fusion-positive prostate cancer, was found to elicit spindle-shaped morphology, faster cell migration and increased cell proliferation, phenotypic changes suggestive of cancer progression. Conclusion: The present findings confirm the value of comprehensive sequencing for biomarker development and provide potential avenues of future study.