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Updated: Aug 9, 2026

Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
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.
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.
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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