Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer

Rohit Mehra, Scott A. Tomlins, Ronglai Shen, Owais Nadeem, Lei Wang, John T. Wei, Kenneth Pienta, Debashis Ghosh, Mark A. Rubin, Arul M. Chinnaiyan, Rajal B. Shah

Research output: Contribution to journalArticle

Abstract

Novel recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS family members ERG, ETV1, or ETV4 have been recently identified as a common molecular event in prostate cancer development. We comprehensively analyzed the frequency and risk of disease progression for the TMPRSS2 and ETS family genes rearrangements in a cohort of 96 American men surgically treated for clinically localized prostate cancer. Using three break apart (TMPRSS2, ERG, ETV4) and one fusion (TMPRSS:ETV1) fluorescence in situ hybridization (FISH) assays, we identified rearrangements in TMPRSS2, ERG, ETV1, and ETV4 in 65, 55, 2, and 2% of cases, respectively. Overall, 54 and 2% of cases demonstrated TMPRSS2:ERG and TMPRSS2:ETV1 fusions, respectively. As intronic loss of genomic DNA between TMPRSS2 and ERG has been identified as a mechanism of TMPRSS2:ERG fusion, our assays allowed us to detect deletion of the 3′ end of TMPRSS2 and the 5′ end of ERG in 41 and 39% of cases rearranged for respective genes. Prostate cancers demonstrating TMPRSS2 gene rearrangement were associated with high pathologic stage (P=0.04). Our results confirm that recurrent chromosomal aberrations in TMPRSS2 and/or ETS family members are found in about 70% of prostate cancers. Importantly, we define a novel approach to study these gene fusions and identified cases where TMPRSS2 was rearranged without rearrangement of ERG, ETV1 or ETV4 and cases with ETS family gene rearrangement without TMPRSS2 rearrangement, suggesting that novel 5′ and 3′ partners may be involved in gene fusions in prostate cancer.

Original languageEnglish (US)
Pages (from-to)538-544
Number of pages7
JournalModern Pathology
Volume20
Issue number5
DOIs
StatePublished - May 30 2007
Externally publishedYes

Fingerprint

Prostatic Neoplasms
Gene Rearrangement
Gene Fusion
Genes
Fluorescence In Situ Hybridization
Chromosome Aberrations
Androgens
Disease Progression
DNA

Keywords

  • Fluorescent in situ hybridization
  • Gene aberrations
  • Localized prostate cancer
  • TMPRSS2, ETS

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Mehra, R., Tomlins, S. A., Shen, R., Nadeem, O., Wang, L., Wei, J. T., ... Shah, R. B. (2007). Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. Modern Pathology, 20(5), 538-544. https://doi.org/10.1038/modpathol.3800769

Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. / Mehra, Rohit; Tomlins, Scott A.; Shen, Ronglai; Nadeem, Owais; Wang, Lei; Wei, John T.; Pienta, Kenneth; Ghosh, Debashis; Rubin, Mark A.; Chinnaiyan, Arul M.; Shah, Rajal B.

In: Modern Pathology, Vol. 20, No. 5, 30.05.2007, p. 538-544.

Research output: Contribution to journalArticle

Mehra, R, Tomlins, SA, Shen, R, Nadeem, O, Wang, L, Wei, JT, Pienta, K, Ghosh, D, Rubin, MA, Chinnaiyan, AM & Shah, RB 2007, 'Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer', Modern Pathology, vol. 20, no. 5, pp. 538-544. https://doi.org/10.1038/modpathol.3800769
Mehra, Rohit ; Tomlins, Scott A. ; Shen, Ronglai ; Nadeem, Owais ; Wang, Lei ; Wei, John T. ; Pienta, Kenneth ; Ghosh, Debashis ; Rubin, Mark A. ; Chinnaiyan, Arul M. ; Shah, Rajal B. / Comprehensive assessment of TMPRSS2 and ETS family gene aberrations in clinically localized prostate cancer. In: Modern Pathology. 2007 ; Vol. 20, No. 5. pp. 538-544.
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abstract = "Novel recurrent gene fusions between the androgen-regulated gene TMPRSS2 and the ETS family members ERG, ETV1, or ETV4 have been recently identified as a common molecular event in prostate cancer development. We comprehensively analyzed the frequency and risk of disease progression for the TMPRSS2 and ETS family genes rearrangements in a cohort of 96 American men surgically treated for clinically localized prostate cancer. Using three break apart (TMPRSS2, ERG, ETV4) and one fusion (TMPRSS:ETV1) fluorescence in situ hybridization (FISH) assays, we identified rearrangements in TMPRSS2, ERG, ETV1, and ETV4 in 65, 55, 2, and 2{\%} of cases, respectively. Overall, 54 and 2{\%} of cases demonstrated TMPRSS2:ERG and TMPRSS2:ETV1 fusions, respectively. As intronic loss of genomic DNA between TMPRSS2 and ERG has been identified as a mechanism of TMPRSS2:ERG fusion, our assays allowed us to detect deletion of the 3′ end of TMPRSS2 and the 5′ end of ERG in 41 and 39{\%} of cases rearranged for respective genes. Prostate cancers demonstrating TMPRSS2 gene rearrangement were associated with high pathologic stage (P=0.04). Our results confirm that recurrent chromosomal aberrations in TMPRSS2 and/or ETS family members are found in about 70{\%} of prostate cancers. Importantly, we define a novel approach to study these gene fusions and identified cases where TMPRSS2 was rearranged without rearrangement of ERG, ETV1 or ETV4 and cases with ETS family gene rearrangement without TMPRSS2 rearrangement, suggesting that novel 5′ and 3′ partners may be involved in gene fusions in prostate cancer.",
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AU - Wei, John T.

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