title: Whole-transcriptome analysis reveals established and novel associations with TMPRSS2:ERG fusion in prostate cancer.
abstract: OBJECTIVE
  Shortcomings of current methods of prostate cancer detection call for improved biomarkers. The transmembrane protease, serine 2:ets-related gene (TMPRSS2:ERG) gene fusion leads to the overexpression of ERG, an E-twenty six (ETS) family transcription factor, and is the most prevalent genetic lesion in prostate cancer, but its clinical utility remains unclear.
  
  
  METHODS
  Two radical prostatectomy samples were analysed by next-generation whole-transcriptome sequencing. The chosen samples differed in fusion gene status, as previously determined by reverse transcription polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Next-generation sequencing identified the involvement of novel and previously reported prostate cancer-related transcripts, the WNT signalling pathway, evasion of p53-mediated anti-proliferation and several ETS-regulated pathways in the prostate cancer cases examined. Overexpression of Rho GDP-dissociation inhibitor (RhoGDIB), a gene associated with fusion-positive prostate cancer, was found to elicit spindle-shaped morphology, faster cell migration and increased cell proliferation, phenotypic changes suggestive of cancer progression.
  
  
  CONCLUSIONS
  The present findings confirm the value of comprehensive sequencing for biomarker development and provide potential avenues of future study.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, ON, Canada.
authors.forename: Anthony
authors.initials: A
authors.lastname: Chow
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Amemiya
authors.forename: Linda
authors.initials: L
authors.lastname: Sugar
authors.forename: Robert
authors.initials: R
authors.lastname: Nam
authors.forename: Arun
authors.initials: A
authors.lastname: Seth
mesh_terms: D001665:Binding Sites; D048708:Cell Growth Processes / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D051155:Wnt1 Protein / Q000096:biosynthesis / Q000235:genetics; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: C403306:EHF protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C495247:WNT1 protein, human; D051155:Wnt1 Protein; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors