Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes

Results from a population-based study of prostate cancer

Liesel M. FitzGerald, Ilir Agalliu, Karynn Johnson, Melinda A. Miller, Erika M. Kwon, Antonio Hurtado-Coll, Ladan Fazli, Ashish B. Rajput, Martin E. Gleave, Michael E. Cox, Elaine A. Ostrander, Janet L. Stanford, David G. Huntsman

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Background: The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. Methods: In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Results: Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22-3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23-3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45-3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). Conclusion: If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.

Original languageEnglish (US)
Article number230
JournalBMC Cancer
Volume8
DOIs
StatePublished - Aug 11 2008

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Gene Fusion
Prostatic Neoplasms
Population
Fluorescence In Situ Hybridization
Single Nucleotide Polymorphism
Survival
Neoplasms
Prostate
Alleles
Phenotype
Recurrence
DNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes : Results from a population-based study of prostate cancer. / FitzGerald, Liesel M.; Agalliu, Ilir; Johnson, Karynn; Miller, Melinda A.; Kwon, Erika M.; Hurtado-Coll, Antonio; Fazli, Ladan; Rajput, Ashish B.; Gleave, Martin E.; Cox, Michael E.; Ostrander, Elaine A.; Stanford, Janet L.; Huntsman, David G.

In: BMC Cancer, Vol. 8, 230, 11.08.2008.

Research output: Contribution to journalArticle

FitzGerald, LM, Agalliu, I, Johnson, K, Miller, MA, Kwon, EM, Hurtado-Coll, A, Fazli, L, Rajput, AB, Gleave, ME, Cox, ME, Ostrander, EA, Stanford, JL & Huntsman, DG 2008, 'Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: Results from a population-based study of prostate cancer', BMC Cancer, vol. 8, 230. https://doi.org/10.1186/1471-2407-8-230
FitzGerald, Liesel M. ; Agalliu, Ilir ; Johnson, Karynn ; Miller, Melinda A. ; Kwon, Erika M. ; Hurtado-Coll, Antonio ; Fazli, Ladan ; Rajput, Ashish B. ; Gleave, Martin E. ; Cox, Michael E. ; Ostrander, Elaine A. ; Stanford, Janet L. ; Huntsman, David G. / Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes : Results from a population-based study of prostate cancer. In: BMC Cancer. 2008 ; Vol. 8.
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abstract = "Background: The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. Methods: In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Results: Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5{\%} were negative and 35.5{\%} were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95{\%} CI = 0.22-3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95{\%} CI = 0.23-3.12) or by the number of retained fusion copies (HR = 1.22, 95{\%} CI = 0.45-3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). Conclusion: If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.",
author = "FitzGerald, {Liesel M.} and Ilir Agalliu and Karynn Johnson and Miller, {Melinda A.} and Kwon, {Erika M.} and Antonio Hurtado-Coll and Ladan Fazli and Rajput, {Ashish B.} and Gleave, {Martin E.} and Cox, {Michael E.} and Ostrander, {Elaine A.} and Stanford, {Janet L.} and Huntsman, {David G.}",
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AU - Agalliu, Ilir

AU - Johnson, Karynn

AU - Miller, Melinda A.

AU - Kwon, Erika M.

AU - Hurtado-Coll, Antonio

AU - Fazli, Ladan

AU - Rajput, Ashish B.

AU - Gleave, Martin E.

AU - Cox, Michael E.

AU - Ostrander, Elaine A.

AU - Stanford, Janet L.

AU - Huntsman, David G.

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N2 - Background: The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. Methods: In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Results: Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22-3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23-3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45-3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). Conclusion: If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.

AB - Background: The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. Methods: In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Results: Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22-3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23-3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45-3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). Conclusion: If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.

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