Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues

Mod Pathol. 2007 Sep;20(9):921-8. doi: 10.1038/modpathol.3800903. Epub 2007 Jul 13.


Recurrent gene fusions between TMPRSS2 and ETS family genes have recently been shown to occur at a high frequency in prostate cancer. In this study, we used formalin-fixed paraffin-embedded tissue and evaluated both TMPRSS2-ERG and TMPRSS2-ETV1 fusions by reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). The results were correlated to overexpression of the downstream ERG and ETV1 sequences. Of 82 cases examined, TMPRSS2-ETV1 fusion was seen in only one case, by FISH. In comparison, TMPRSS2-ERG fusion was documented in 35 cases (43%) by either RT-PCR or FISH. Deletion, rather than translocation, was found to be the main mechanism for TMPRSS2-ERG gene fusion (81 vs 19%). RT-PCR and FISH results correlated well, with most positive cases resulting in overexpression of downstream ERG sequences. Several TMPRSS2-ERG fusion transcript variants were identified, most of which are predicted to encode truncated ERG proteins. Prostate cancer of Gleason's scores 6 or 7 had more frequent TMPRSS2-ERG fusions than higher-grade tumors, but this difference was not statistically significant (P=0.42). On the other hand, mucin-positive carcinomas more often harbor such gene fusions when compared to mucin-negative tumors (P=0.004). These morphological correlates, and more importantly the potential correlation of such fusions to clinical outcome and treatment responses, should be further explored.

Publication types

  • Comparative Study

MeSH terms

  • DNA-Binding Proteins / genetics*
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic
  • Gene Fusion*
  • Humans
  • In Situ Hybridization, Fluorescence*
  • Male
  • Neoplasm Staging
  • Oncogene Proteins, Fusion / genetics*
  • Paraffin Embedding
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • RNA / analysis
  • Reverse Transcriptase Polymerase Chain Reaction*
  • Serine Endopeptidases / genetics*
  • Trans-Activators / genetics*
  • Transcription Factors / genetics*
  • Transcriptional Regulator ERG
  • Translocation, Genetic


  • DNA-Binding Proteins
  • ERG protein, human
  • ETV1 protein, human
  • Oncogene Proteins, Fusion
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Regulator ERG
  • RNA
  • Serine Endopeptidases
  • TMPRSS2 protein, human