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Open Access Highly Accessed Research article

TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling

Jan C Brase1, Marc Johannes1, Heiko Mannsperger2, Maria Fälth1, Jennifer Metzger1, Lukasz A Kacprzyk1, Tatjana Andrasiuk1, Stephan Gade1, Michael Meister3, Hüseyin Sirma4, Guido Sauter4, Ronald Simon4, Thorsten Schlomm5, Tim Beißbarth6, Ulrike Korf2, Ruprecht Kuner1 and Holger Sültmann1*

Author Affiliations

1 Unit Cancer Genome Research, Division of Molecular Genetics, German Cancer Research Center and National Center for Tumor Diseases, Im Neuenheimer Feld 460, 69120 Heidelberg, Germany

2 Division of Molecular Genome Analysis, German Cancer Research Center, Heidelberg, Germany

3 Translational Research Unit, Thoraxklinik, University of Heidelberg, Heidelberg, Germany

4 Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

5 Martini-Clinic, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

6 Department Medical Statistics, University Medical Center Göttingen, Göttingen, Germany

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BMC Cancer 2011, 11:507  doi:10.1186/1471-2407-11-507

Published: 5 December 2011

Abstract

Background

TMPRSS2-ERG gene fusions occur in about 50% of all prostate cancer cases and represent promising markers for molecular subtyping. Although TMPRSS2-ERG fusion seems to be a critical event in prostate cancer, the precise functional role in cancer development and progression is still unclear.

Methods

We studied large-scale gene expression profiles in 47 prostate tumor tissue samples and in 48 normal prostate tissue samples taken from the non-suspect area of clinical low-risk tumors using Affymetrix GeneChip Exon 1.0 ST microarrays.

Results

Comparison of gene expression levels among TMPRSS2-ERG fusion-positive and negative tumors as well as benign samples demonstrated a distinct transcriptional program induced by the gene fusion event. Well-known biomarkers for prostate cancer detection like CRISP3 were found to be associated with the gene fusion status. WNT and TGF-β/BMP signaling pathways were significantly associated with genes upregulated in TMPRSS2-ERG fusion-positive tumors.

Conclusions

The TMPRSS2-ERG gene fusion results in the modulation of transcriptional patterns and cellular pathways with potential consequences for prostate cancer progression. Well-known biomarkers for prostate cancer detection were found to be associated with the gene fusion. Our results suggest that the fusion status should be considered in retrospective and future studies to assess biomarkers for prostate cancer detection, progression and targeted therapy.

Keywords:
Prostate cancer; TMPRSS2-ERG; Gene expression profiling