Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Aug 11:8:230.
doi: 10.1186/1471-2407-8-230.

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

Liesel M FitzGerald  1 , 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
Affiliations

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

Liesel M FitzGerald et al. BMC Cancer. .

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Relative locations of BAC probes on chr21q22 for FISH assays. A) Normal chromosome. B) TMPRSS2-ERG fusion by translocation. C) TMPRSS2-ERG fusion by deletion.
Figure 2
Figure 2
FISH detection of TMPRSS2 and ERG gene status. A) No TMPRSS2-ERG fusion. B) Positive for the TMPRSS2-ERG fusion with translocation – arrows indicate the separate green 5' ERG signal. C) Positive for the TMPRSS2-ERG fusion with deletion – arrows indicate the combined blue/red TMPRSS2 and 3' ERG signal and the absence of the green 5' ERG signal. FISH signals in these pseudo-colored images are red (telomeric to TMPRSS2; RP11-35C4), green (5' ERG; RP11-95I21) and blue (3' ERG; RP11-476D17). Note that in non-rearranged chromosomes the proximity of the green and blue signals can result in an aqua-colored signal.
Figure 3
Figure 3
Kaplan-Meier survival estimates. A) Patients with and without TMPRSS2-ERG gene fusion. B) Patients with no TMPRSS2-ERG fusion, patients with fusion by translocation and patients with fusion by deletion. C) Patients with no TMPRSS2-ERG fusion, patients with a single fusion and patients with multiple fusions.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Petrovics G, Liu A, Shaheduzzaman S, Furusato B, Sun C, Chen Y, Nau M, Ravindranath L, Chen Y, Dobi A, Srikantan V, Sesterhenn IA, McLeod DG, Vahey M, Moul JW, Srivastava S. Frequent overexpression of ETS-related gene-1 (ERG1) in prostate cancer transcriptome. Oncogene. 2005;24:3847–3852. doi: 10.1038/sj.onc.1208518. - DOI - PubMed
    1. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310:644–648. doi: 10.1126/science.1117679. - DOI - PubMed
    1. Cerveira N, Ribeiro FR, Peixoto A, Costa V, Henrique R, Jeronimo C, Teixeira MR. TMPRSS2-ERG gene fusion causing ERG overexpression precedes chromosome copy number changes in prostate carcinomas and paired HGPIN lesions. Neoplasia. 2006;8:826–832. doi: 10.1593/neo.06427. - DOI - PMC - PubMed
    1. Nam RK, Sugar L, Yang W, Srivastava S, Klotz LH, Yang LY, Stanimirovic A, Encioiu E, Neill M, Loblaw DA, Trachtenberg J, Narod SA, Seth A. Expression of the TMPRSS2:ERG fusion gene predicts cancer recurrence after surgery for localised prostate cancer. Br J Cancer. 2007;97:1690–1695. doi: 10.1038/sj.bjc.6604054. - DOI - PMC - PubMed
    1. Perner S, Demichelis F, Beroukhim R, Schmidt FH, Mosquera JM, Setlur S, Tchinda J, Tomlins SA, Hofer MD, Pienta KG, Kuefer R, Vessella R, Sun XW, Meyerson M, Lee C, Sellers WR, Chinnaiyan AM, Rubin MA. TMPRSS2:ERG fusion-associated deletions provide insight into the heterogeneity of prostate cancer. Cancer Res. 2006;66:8337–8341. doi: 10.1158/0008-5472.CAN-06-1482. - DOI - PubMed

Publication types

Substances