Whole-transcriptome analysis reveals established and novel associations with TMPRSS2:ERG fusion in prostate cancer

Anticancer Res. 2012 Sep;32(9):3629-41.

Abstract

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 in fusion 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Growth Processes / physiology
  • Cell Movement / physiology
  • HEK293 Cells
  • Humans
  • Male
  • Oncogene Proteins, Fusion / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptome
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics
  • Wnt1 Protein / biosynthesis
  • Wnt1 Protein / genetics
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors / biosynthesis
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors / genetics
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors / metabolism

Substances

  • EHF protein, human
  • Oncogene Proteins, Fusion
  • TMPRSS2-ERG fusion protein, human
  • TP53 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • WNT1 protein, human
  • Wnt1 Protein
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors