Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Communication
  • Published:

Diversity of TMPRSS2-ERG fusion transcripts in the human prostate

Abstract

TMPRSS2-ERG gene fusions have recently been reported to be present in a high proportion of human prostate cancers. In the current study, we show that great diversity exists in the precise structure of TMPRSS2-ERG hybrid transcripts found in human prostates. Fourteen distinct hybrid transcripts are characterized, each containing different combinations of sequences from the TMPRSS2 and ERG genes. The transcripts include two that are predicted to encode a normal full-length ERG protein, six that encode N-terminal truncated ERG proteins and one that encodes a TMPRSS2-ERG fusion protein. Interestingly, distinct patterns of hybrid transcripts were found in samples taken from separate regions of individual cancer-containing prostates, suggesting that TMPRSS2-ERG gene fusions may be arising independently in different regions of a single prostate.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Carney DN, Gazdar AF, Bepler G, Guccion JG, Marangos PJ, Moody TW et al. (1985). Establishment and identification of small cell lung cancer cell lines having classic and variant features. Cancer Res 45: 2913–2923.

    CAS  PubMed  Google Scholar 

  • Clark J, Rocques PJ, Crew AJ, Gill S, Shipley J, Chan AM et al. (1994). Identification of novel genes, SYT and SSX, involved in the t(X;18)(p11.2;q11.2) translocation found in human synovial sarcoma. Nat Genet 7: 502–508.

    Article  CAS  Google Scholar 

  • Cooper CS (ed). (2001). Translocations in Solid Tumours. Landes Biosciences: Texas, USA.

    Google Scholar 

  • de Alava E, Kawai A, Healey JH, Fligman I, Meyers PA, Huvos AG et al. (1998). EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma. J Clin Oncol 16: 1248–1255.

    Article  CAS  Google Scholar 

  • Delattre O, Sevenet N . (2002). Chromosomes Translocations in the Ewing Family of Tumors. Landes Bioscience: Texas, USA.

    Google Scholar 

  • Ichikawa H, Shimizu K, Hayashi Y, Ohki M . (1994). An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation. Cancer Res 54: 2865–2868.

    CAS  PubMed  Google Scholar 

  • Janknecht R . (2005). EWS-ETS oncoproteins: the linchpins of Ewing tumors. Gene 363: 1–14.

    Article  CAS  Google Scholar 

  • Jhavar SG, Fisher C, Jackson A, Reinsberg SA, Dennis N, Falconer A et al. (2005). Processing of radical prostatectomy specimens for correlation of data from histopathological, molecular biological, and radiological studies: a new whole organ technique. J Clin Pathol 58: 504–508.

    Article  CAS  Google Scholar 

  • Kojima T, Asami S, Chin M, Yoshida Y, Mugishima H, Suzuki T . (2002). Detection of chimeric genes in Ewing's sarcoma and its clinical applications. Biol Pharm Bull 25: 991–994.

    Article  CAS  Google Scholar 

  • Kong XT, Ida K, Ichikawa H, Shimizu K, Ohki M, Maseki N et al. (1997). Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript. Blood 90: 1192–1199.

    CAS  PubMed  Google Scholar 

  • Lin PP, Brody RI, Hamelin AC, Bradner JE, Healey JH, Ladanyi M . (1999). Differential transactivation by alternative EWS-FLI1 fusion proteins correlates with clinical heterogeneity in Ewing's sarcoma. Cancer Res 59: 1428–1432.

    CAS  PubMed  Google Scholar 

  • Lykke-Andersen J, Shu MD, Steitz JA . (2000). Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell 103: 1121–1131.

    Article  CAS  Google Scholar 

  • Sharrocks AD . (2001). The ETS-domain transcription factor family. Nat Rev Mol Cell Biol 2: 827–837.

    Article  CAS  Google Scholar 

  • Soller MJ, Isaksson M, Elfving P, Soller W, Lundgren R, Panagopoulos I . (2006). Confirmation of the high frequency of the TMPRSS2/ERG fusion gene in prostate cancer. Genes Chromosomes Cancer 45: 717–719.

    Article  CAS  Google Scholar 

  • Tomlins SA, Mehra R, Rhodes DR, Smith LR, Roulston D, Helgeson BE et al. (2006). TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. Cancer Res 66: 3396–3400.

    Article  CAS  Google Scholar 

  • Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW et al. (2005). Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 310: 644–648.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded by Cancer Research UK, the National Cancer Research Institute, the Grand Charity of Freemasons and the Rosetrees Trust. We thank Christine Bell for help with typing the manuscript. This work was approved by the Clinical Research and Ethics Committee at the Royal Marsden NHS Foundation Trust and Institute of Cancer Research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J Clark.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clark, J., Merson, S., Jhavar, S. et al. Diversity of TMPRSS2-ERG fusion transcripts in the human prostate. Oncogene 26, 2667–2673 (2007). https://doi.org/10.1038/sj.onc.1210070

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1210070

Keywords

This article is cited by

Search

Quick links