TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer

Cancer Res. 2006 Apr 1;66(7):3396-400. doi: 10.1158/0008-5472.CAN-06-0168.

Abstract

Although common in hematologic and mesenchymal malignancies, recurrent gene fusions have not been well characterized in epithelial carcinomas. Recently, using a novel bioinformatic approach, we identified recurrent gene fusions between TMPRSS2 and the ETS family members ERG or ETV1 in the majority of prostate cancers. Here, we interrogated the expression of all ETS family members in prostate cancer profiling studies and identified marked overexpression of ETV4 in 2 of 98 cases. In one such case, we confirmed the overexpression of ETV4 using quantitative PCR, and by rapid amplification of cDNA ends, quantitative PCR, and fluorescence in situ hybridization, we show that the TMPRSS2 (21q22) and ETV4 (17q21) loci are fused in this case. This result defines a third molecular subtype of prostate cancer and supports the hypothesis that dysregulation of ETS family members through fusions with TMRPSS2 may be an initiating event in prostate cancer development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenovirus E1A Proteins / biosynthesis
  • Adenovirus E1A Proteins / genetics*
  • Base Sequence
  • Gene Expression Profiling
  • Gene Fusion*
  • Humans
  • Male
  • Molecular Sequence Data
  • Oncogene Proteins, Fusion / biosynthesis
  • Oncogene Proteins, Fusion / genetics*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-ets
  • Serine Endopeptidases / biosynthesis
  • Serine Endopeptidases / genetics*

Substances

  • Adenovirus E1A Proteins
  • ETV4 protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • TMPRSS2-ETV4 fusion protein, human
  • Serine Endopeptidases
  • TMPRSS2 protein, human

Associated data

  • GENBANK/DQ396625
  • GENBANK/DQ396626