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Open Access Highly Accessed Research article

Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer

Liesel M FitzGerald1, Ilir Agalliu12, Karynn Johnson3, Melinda A Miller4, Erika M Kwon5, Antonio Hurtado-Coll3, Ladan Fazli3, Ashish B Rajput3, Martin E Gleave3, Michael E Cox3, Elaine A Ostrander5, Janet L Stanford16 and David G Huntsman34*

Author Affiliations

1 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N., Seattle, WA 98109, USA

2 Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA

3 The Prostate Research Centre, Vancouver General Hospital, Vancouver, BC V6H-3Z6, Canada

4 The Centre for Translational and Applied Genomics, British Columbia Cancer Agency, Vancouver, BC V5Z-4E6, Canada

5 National Human Genome Institute, Cancer Genetics Branch, National Institutes of Health, Building 50, 50 South Drive, Bethesda, MD 20892, USA

6 Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, Washington, USA

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BMC Cancer 2008, 8:230  doi:10.1186/1471-2407-8-230

Published: 11 August 2008

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.