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

Scott A Tomlins1, Rohit Mehra, Daniel R Rhodes

  • 1Department of Pathology, University of Michigan Medical School, 1301 Catherine Street, Ann Arbor, MI 48109, USA.

Cancer Research
|April 6, 2006
PubMed

Insights

Researchers discovered a new gene fusion in prostate cancer involving TMPRSS2 and ETV4. This finding identifies a third molecular subtype of prostate cancer and suggests ETS gene fusions are key to its development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Recurrent gene fusions are common in certain cancers but less understood in epithelial carcinomas.
  • Previous research identified TMPRSS2-ERG and TMPRSS2-ETV1 gene fusions in most prostate cancers.

Purpose of the Study:

  • To investigate ETS family member expression in prostate cancer.
  • To identify novel gene fusions in prostate cancer beyond those previously characterized.

Main Methods:

  • Bioinformatic analysis of prostate cancer profiling data.
  • Quantitative PCR (qPCR) for gene expression validation.
  • Rapid amplification of cDNA ends (RACE) and fluorescence in situ hybridization (FISH) for fusion confirmation.

Main Results:

  • Identified overexpression of ETV4 in 2 out of 98 prostate cancer cases.
  • Confirmed a novel TMPRSS2-ETV4 gene fusion in one case.
  • This fusion involves the TMPRSS2 locus at 21q22 and the ETV4 locus at 17q21.

Conclusions:

  • The TMPRSS2-ETV4 fusion defines a third molecular subtype of prostate cancer.
  • Dysregulation of ETS family members via TMPRSS2 fusions is implicated as an initiating event in prostate cancer.

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