Frequency of the TMPRSS2: ERG gene fusion is increased in moderate to poorly differentiated prostate cancers

Ashish B. Rajput, Melinda A. Miller, Alessandro De Luca, Niki Boyd, Sam Leung, Antonio Hurtado-Coll, Ladan Fazli, Edward C. Jones, Jodie B. Palmer, Martin E. Gleave, Michael E. Cox, David G. Huntsman

Research output: Contribution to journalArticle

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Abstract

Background: Recent reports indicate that prostate cancers (CaP) frequently over-express the potential oncogenes, ERG or ETV1. Many cases have chromosomal rearrangements leading to the fusion of the 5′ end of the androgen-regulated serine protease TMPRSS2 (21q22.2) to the 3′ end of either ERG (21q22.3) or ETV1 (7p21.3). The consequence of these rearrangements is aberrant androgen receptor-driven expression of the potential oncogenes, ETV1 or ERG. Aim: To determine the frequency of rearrangements involving TMPRSS2, ERG, or ETV1 genes in CaP of varying Gleason grades through fluorescence in situ hybridisation (FISH) on CaP tissue microarrays (TMAs). Methods: Two independent assays, a TMPRSS2 break-apart assay and a three-colour gene fusion FISH assay were applied to TMAs. FISH positive cases were confirmed by reverse transcriptase (RT) PCR and DNA sequence analysis. Results: A total of 106/196 (54.1%) cases were analysed by FISH. None of the five benign prostatic hyperplasia cases analysed exhibited these gene rearrangements. TMPRSS2:ERG fusion was found more frequently in moderate to poorly differentiated tumours (35/86, 40.7%) than in well differentiated tumours (1/15, 6.7%, p = 0.017). TMPRSS2:ETV1 gene fusions were not detected in any of the cases tested. TMPRSS2:ERG fusion product was verified by RT-PCR followed by DNA sequencing in 7/7 randomly selected positive cases analysed. Conclusion: This study indicates that TMPRSS2:ERG gene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub-classifications of these cancers.

Original languageEnglish
Pages (from-to)1238-1243
Number of pages6
JournalJournal of Clinical Pathology
Volume60
Issue number11
DOIs
Publication statusPublished - Nov 2007

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Gene Fusion
Fluorescence In Situ Hybridization
Prostatic Neoplasms
Gene Rearrangement
Reverse Transcriptase Polymerase Chain Reaction
DNA Sequence Analysis
Oncogenes
Neoplasms
Androgen Receptors
Prostatic Hyperplasia
Serine Proteases
Androgens
Color
Genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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Frequency of the TMPRSS2 : ERG gene fusion is increased in moderate to poorly differentiated prostate cancers. / Rajput, Ashish B.; Miller, Melinda A.; De Luca, Alessandro; Boyd, Niki; Leung, Sam; Hurtado-Coll, Antonio; Fazli, Ladan; Jones, Edward C.; Palmer, Jodie B.; Gleave, Martin E.; Cox, Michael E.; Huntsman, David G.

In: Journal of Clinical Pathology, Vol. 60, No. 11, 11.2007, p. 1238-1243.

Research output: Contribution to journalArticle

Rajput, AB, Miller, MA, De Luca, A, Boyd, N, Leung, S, Hurtado-Coll, A, Fazli, L, Jones, EC, Palmer, JB, Gleave, ME, Cox, ME & Huntsman, DG 2007, 'Frequency of the TMPRSS2: ERG gene fusion is increased in moderate to poorly differentiated prostate cancers', Journal of Clinical Pathology, vol. 60, no. 11, pp. 1238-1243. https://doi.org/10.1136/jcp.2006.043810
Rajput, Ashish B. ; Miller, Melinda A. ; De Luca, Alessandro ; Boyd, Niki ; Leung, Sam ; Hurtado-Coll, Antonio ; Fazli, Ladan ; Jones, Edward C. ; Palmer, Jodie B. ; Gleave, Martin E. ; Cox, Michael E. ; Huntsman, David G. / Frequency of the TMPRSS2 : ERG gene fusion is increased in moderate to poorly differentiated prostate cancers. In: Journal of Clinical Pathology. 2007 ; Vol. 60, No. 11. pp. 1238-1243.
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abstract = "Background: Recent reports indicate that prostate cancers (CaP) frequently over-express the potential oncogenes, ERG or ETV1. Many cases have chromosomal rearrangements leading to the fusion of the 5′ end of the androgen-regulated serine protease TMPRSS2 (21q22.2) to the 3′ end of either ERG (21q22.3) or ETV1 (7p21.3). The consequence of these rearrangements is aberrant androgen receptor-driven expression of the potential oncogenes, ETV1 or ERG. Aim: To determine the frequency of rearrangements involving TMPRSS2, ERG, or ETV1 genes in CaP of varying Gleason grades through fluorescence in situ hybridisation (FISH) on CaP tissue microarrays (TMAs). Methods: Two independent assays, a TMPRSS2 break-apart assay and a three-colour gene fusion FISH assay were applied to TMAs. FISH positive cases were confirmed by reverse transcriptase (RT) PCR and DNA sequence analysis. Results: A total of 106/196 (54.1{\%}) cases were analysed by FISH. None of the five benign prostatic hyperplasia cases analysed exhibited these gene rearrangements. TMPRSS2:ERG fusion was found more frequently in moderate to poorly differentiated tumours (35/86, 40.7{\%}) than in well differentiated tumours (1/15, 6.7{\%}, p = 0.017). TMPRSS2:ETV1 gene fusions were not detected in any of the cases tested. TMPRSS2:ERG fusion product was verified by RT-PCR followed by DNA sequencing in 7/7 randomly selected positive cases analysed. Conclusion: This study indicates that TMPRSS2:ERG gene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub-classifications of these cancers.",
author = "Rajput, {Ashish B.} and Miller, {Melinda A.} and {De Luca}, Alessandro and Niki Boyd and Sam Leung and Antonio Hurtado-Coll and Ladan Fazli and Jones, {Edward C.} and Palmer, {Jodie B.} and Gleave, {Martin E.} and Cox, {Michael E.} and Huntsman, {David G.}",
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T2 - ERG gene fusion is increased in moderate to poorly differentiated prostate cancers

AU - Rajput, Ashish B.

AU - Miller, Melinda A.

AU - De Luca, Alessandro

AU - Boyd, Niki

AU - Leung, Sam

AU - Hurtado-Coll, Antonio

AU - Fazli, Ladan

AU - Jones, Edward C.

AU - Palmer, Jodie B.

AU - Gleave, Martin E.

AU - Cox, Michael E.

AU - Huntsman, David G.

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N2 - Background: Recent reports indicate that prostate cancers (CaP) frequently over-express the potential oncogenes, ERG or ETV1. Many cases have chromosomal rearrangements leading to the fusion of the 5′ end of the androgen-regulated serine protease TMPRSS2 (21q22.2) to the 3′ end of either ERG (21q22.3) or ETV1 (7p21.3). The consequence of these rearrangements is aberrant androgen receptor-driven expression of the potential oncogenes, ETV1 or ERG. Aim: To determine the frequency of rearrangements involving TMPRSS2, ERG, or ETV1 genes in CaP of varying Gleason grades through fluorescence in situ hybridisation (FISH) on CaP tissue microarrays (TMAs). Methods: Two independent assays, a TMPRSS2 break-apart assay and a three-colour gene fusion FISH assay were applied to TMAs. FISH positive cases were confirmed by reverse transcriptase (RT) PCR and DNA sequence analysis. Results: A total of 106/196 (54.1%) cases were analysed by FISH. None of the five benign prostatic hyperplasia cases analysed exhibited these gene rearrangements. TMPRSS2:ERG fusion was found more frequently in moderate to poorly differentiated tumours (35/86, 40.7%) than in well differentiated tumours (1/15, 6.7%, p = 0.017). TMPRSS2:ETV1 gene fusions were not detected in any of the cases tested. TMPRSS2:ERG fusion product was verified by RT-PCR followed by DNA sequencing in 7/7 randomly selected positive cases analysed. Conclusion: This study indicates that TMPRSS2:ERG gene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub-classifications of these cancers.

AB - Background: Recent reports indicate that prostate cancers (CaP) frequently over-express the potential oncogenes, ERG or ETV1. Many cases have chromosomal rearrangements leading to the fusion of the 5′ end of the androgen-regulated serine protease TMPRSS2 (21q22.2) to the 3′ end of either ERG (21q22.3) or ETV1 (7p21.3). The consequence of these rearrangements is aberrant androgen receptor-driven expression of the potential oncogenes, ETV1 or ERG. Aim: To determine the frequency of rearrangements involving TMPRSS2, ERG, or ETV1 genes in CaP of varying Gleason grades through fluorescence in situ hybridisation (FISH) on CaP tissue microarrays (TMAs). Methods: Two independent assays, a TMPRSS2 break-apart assay and a three-colour gene fusion FISH assay were applied to TMAs. FISH positive cases were confirmed by reverse transcriptase (RT) PCR and DNA sequence analysis. Results: A total of 106/196 (54.1%) cases were analysed by FISH. None of the five benign prostatic hyperplasia cases analysed exhibited these gene rearrangements. TMPRSS2:ERG fusion was found more frequently in moderate to poorly differentiated tumours (35/86, 40.7%) than in well differentiated tumours (1/15, 6.7%, p = 0.017). TMPRSS2:ETV1 gene fusions were not detected in any of the cases tested. TMPRSS2:ERG fusion product was verified by RT-PCR followed by DNA sequencing in 7/7 randomly selected positive cases analysed. Conclusion: This study indicates that TMPRSS2:ERG gene rearrangements in CaP may be used as a diagnostic tool to identify prognostically relevant sub-classifications of these cancers.

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