title: Integration of ERG gene mapping and gene-expression profiling identifies distinct categories of human prostate cancer.
abstract: OBJECTIVE
  To integrate the mapping of ERG alterations with the collection of expression microarray (EMA) data, as previous EMA analyses have failed to consider the genetic heterogeneity and complex patterns of ERG alteration frequently found in cancerous prostates.
  
  
  METHODS
  We determined genome-wide expression levels with GeneChip Human Exon 1.0 ST arrays (Affymetrix, Santa Clara, CA, USA) using RNA prepared from 35 specimens of prostate cancer from 28 prostates.
  
  
  RESULTS
  The expression profiles showed clustering, in unsupervised hierarchical analyses, into two distinct prostate cancer categories, with one group strongly associated with indicators of poor clinical outcome. The two categories are not tightly linked to ERG status. By analysis of the data we identified a subgroup of cancers lacking ERG rearrangements that showed an outlier pattern of SPINK1 mRNA expression. There was a major distinction between ERG rearranged and non-rearranged cancers that involves the levels of expression of genes linked to exposure to beta-oestradiol, and to retinoic acid.
  
  
  CONCLUSIONS
  Expression profiling of prostate cancer samples containing single patterns of ERG alterations can provide novel insights into the mechanism of prostate cancer development, and support the view that factors other than ERG status are the major determinants of poor clinical outcome.
authors.affiliation: Institute of Cancer Research, Male Urological Cancer Research Centre, Sutton, Surrey, UK.
authors.forename: Sameer
authors.initials: S
authors.lastname: Jhavar
authors.forename: Daniel
authors.initials: D
authors.lastname: Brewer
authors.forename: Sandra
authors.initials: S
authors.lastname: Edwards
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.forename: Jeremy
authors.initials: J
authors.lastname: Clark
authors.forename: Penny
authors.initials: P
authors.lastname: Flohr
authors.forename: Timothy
authors.initials: T
authors.lastname: Christmas
authors.forename: Alan
authors.initials: A
authors.lastname: Thompson
authors.forename: Matthew
authors.initials: M
authors.lastname: Parker
authors.forename: Christopher
authors.initials: C
authors.lastname: Shepherd
authors.forename: Ulf-Hakan
authors.initials: UH
authors.lastname: Stenman
authors.forename: Tania
authors.initials: T
authors.lastname: Marchbank
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Playford
authors.forename: Christopher
authors.initials: C
authors.lastname: Woodhouse
authors.forename: Christopher
authors.initials: C
authors.lastname: Ogden
authors.forename: Cyril
authors.initials: C
authors.lastname: Fisher
authors.forename: Gyula
authors.initials: G
authors.lastname: Kovacs
authors.forename: Cathy
authors.initials: C
authors.lastname: Corbishley
authors.forename: Charles
authors.initials: C
authors.lastname: Jameson
authors.forename: Andy
authors.initials: A
authors.lastname: Norman
authors.forename: Johann
authors.initials: J
authors.lastname: De-Bono
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
authors.forename: Rosalind
authors.initials: R
authors.lastname: Eeles
authors.forename: Colin S
authors.initials: CS
authors.lastname: Cooper
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic
chemical_list: D002352:Carrier Proteins; C072312:ERG protein, human; C486642:SPINK1 protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic