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. 2011 Dec 5:11:507.
doi: 10.1186/1471-2407-11-507.

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

Jan C Brase  1 , Marc Johannes, Heiko Mannsperger, Maria Fälth, Jennifer Metzger, Lukasz A Kacprzyk, Tatjana Andrasiuk, Stephan Gade, Michael Meister, Hüseyin Sirma, Guido Sauter, Ronald Simon, Thorsten Schlomm, Tim Beissbarth, Ulrike Korf, Ruprecht Kuner, Holger Sültmann
Affiliations

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

Jan C Brase et al. BMC Cancer. .

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.

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Figures

Figure 1
Figure 1
TMPRSS2-ERG specific transcriptional modulations. Clustering of 48 benign (light green), 20 fusion-negative (dark green) and 17 fusion-positive (red) prostate cancer tissue samples. Clustering is based on the expression levels of 126 genes, which showed at least 2-fold expression changes (Additional file 4: Table S4) between the TMPRSS-ERG positive and negative subgroups. Expression values are color-coded (red = upregulation; blue = downregulation).
Figure 2
Figure 2
Overlap of prostate cancer and TMPRSS2-ERG biomarkers. Significant genes with at least 2-fold expression changes in the tumor-normal comparison (blue, Additional file 3: Table S3) and the TMPRSS2-ERG subgroups (yellow, Additional file 4: Table S4).
Figure 3
Figure 3
Association between biomarkers for prostate cancer detection and TMPRSS2-ERG gene fusion. Gene expression of TDRD1 (A) and CRISP3 (B) in 48 benign, 47 tumor (left side) as well as in the TMPRSS2-ERG (20 fusion-negative vs. 17 fusion-positive tumor samples; right side).
See this image and copyright information in PMC

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