TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling
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
BMC Cancer 2011, 11:507 doi:10.1186/1471-2407-11-507Published: 5 December 2011
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.
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.
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.
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.