title: TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling.
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.
authors.affiliation: 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.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Brase
authors.forename: Marc
authors.initials: M
authors.lastname: Johannes
authors.forename: Heiko
authors.initials: H
authors.lastname: Mannsperger
authors.forename: Maria
authors.initials: M
authors.lastname: Fälth
authors.forename: Jennifer
authors.initials: J
authors.lastname: Metzger
authors.forename: Lukasz A
authors.initials: LA
authors.lastname: Kacprzyk
authors.forename: Tatjana
authors.initials: T
authors.lastname: Andrasiuk
authors.forename: Stephan
authors.initials: S
authors.lastname: Gade
authors.forename: Michael
authors.initials: M
authors.lastname: Meister
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Sirma
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Tim
authors.initials: T
authors.lastname: Beissbarth
authors.forename: Ulrike
authors.initials: U
authors.lastname: Korf
authors.forename: Ruprecht
authors.initials: R
authors.lastname: Kuner
authors.forename: Holger
authors.initials: H
authors.lastname: Sültmann
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D050939:Gene Fusion; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D012334:RNA, Neoplasm / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; D012334:RNA, Neoplasm; C515553:TMPRSS2-ERG fusion protein, human; D016212:Transforming Growth Factor beta