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

FitzGerald, Liesel M and Agalliu, Ilir and Johnson, Karynn and Miller, Melinda A and Kwon, Erika M and Hurtado-Coll, Antonio and Fazli, Ladan and Rajput, Ashish B and Gleave, Martin E and Cox, Michael E and Ostrander, Elaine A and Stanford, Janet L and Huntsman, David G (2008) Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer. BMC Cancer, 8. ISSN 1471-2407

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Article URL: http://www.biomedcentral.com/1471-2407/8/230

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.

Item Type: Article
DOI: 10.1186/1471-2407-8-230
PubMed ID: 18694509
PMCID: PMC2519091
Grant Numbers: RO1 CA56678, RO1 CA114524, P50 CA97186
Keywords or MeSH Headings: Adult Aged Aged, 80 and over Genotype Humans In Situ Hybridization, Fluorescence Male Microarray Analysis Middle Aged Oncogene Fusion Oncogene Proteins, Fusion/genetics* Oncogene Proteins, Fusion/physiology* Polymorphism, Single Nucleotide Prostatectomy Prostatic Neoplasms/metabolism* Prostatic Neoplasms/pathology Treatment Outcome
Subjects: Cellular and Organismal Processes > Genetic processes > DNA rearrangement
Research Methodologies > Epidemiology > Risk assessment
Diseases > Solid tumors > Prostate cancer
Depositing User: authors@FHCRC Administrator-Import
Date Deposited: 04 Sep 2008 20:40
Last Modified: 14 Feb 2012 14:42
URI: http://authors.fhcrc.org/id/eprint/22

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