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

BMC Cancer

Holger Sültmann⁴  Ruprecht Kuner⁴  Ulrike Korf²  Tim Beißbarth¹  Thorsten Schlomm⁵  Ronald Simon³  Guido Sauter³  Hüseyin Sirma³  Michael Meister⁶  Stephan Gade⁴  Tatjana Andrasiuk⁴  Lukasz A Kacprzyk⁴  Jennifer Metzger⁴  Maria Fälth⁴  Heiko Mannsperger²  Marc Johannes⁴  Jan C Brase⁴ 

[1]Department Medical Statistics, University Medical Center Göttingen, Göttingen, Germany

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

[3]Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

[4]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

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

[6]Translational Research Unit, Thoraxklinik, University of Heidelberg, Heidelberg, Germany

关键词: Gene expression profiling;    TMPRSS2-ERG;    Prostate cancer;   

Others  :  1080628
DOI  :  10.1186/1471-2407-11-507

 received in 2011-06-09, accepted in 2011-12-05,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Brase et al.; licensee BioMed Central Ltd.

【 图 表 】

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