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

• Main Authors: Brase Jan C, Johannes Marc, Mannsperger Heiko, Fälth Maria, Metzger Jennifer, Kacprzyk Lukasz A, Andrasiuk Tatjana, Gade Stephan, Meister Michael, Sirma Hüseyin, Sauter Guido, Simon Ronald, Schlomm Thorsten, Beißbarth Tim, Korf Ulrike, Kuner Ruprecht, Sültmann Holger
• Format: Article
• Language: English
• Published: BMC 2011-12-01
• Series: BMC Cancer
• Subjects: Prostate cancer; <it>TMPRSS2-ERG</it>; Gene expression profiling
• Online Access: http://www.biomedcentral.com/1471-2407/11/507

<p>Abstract</p> <p>Background</p> <p><it>TMPRSS2-ERG </it>gene fusions occur in about 50% of all prostate cancer cases and represent promising markers for molecular subtyping. Although <it>TMPRSS2-ERG </it>fusion seems to be a critical event in prostate cancer, the precise functional role in cancer development and progression is still unclear.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>Comparison of gene expression levels among <it>TMPRSS2-ERG </it>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 <it>CRISP3 </it>were found to be associated with the gene fusion status. WNT and TGF-β/BMP signaling pathways were significantly associated with genes upregulated in <it>TMPRSS2-ERG </it>fusion-positive tumors.</p> <p>Conclusions</p> <p>The <it>TMPRSS2-ERG </it>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.</p>