Integration of ERG gene mapping and gene-expression profiling identifies distinct categories of human prostate cancer

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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. MATERIALS AND 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.

Detaljer

Författare
  • Sameer Jhavar
  • Daniel Brewer
  • Sandra Edwards
  • Zsofia Kote-Jarai
  • Gerhardt Attard
  • Jeremy Clark
  • Penny Flohr
  • Timothy Christmas
  • Alan Thompson
  • Matthew Parker
  • Christopher Shepherd
  • Ulf-Hakan Stenman
  • Tania Marchbank
  • Raymond J. Playford
  • Christopher Woodhouse
  • Christopher Ogden
  • Cyril Fisher
  • Gyula Kovacs
  • Cathy Corbishley
  • Charles Jameson
  • Andy Norman
  • Johann De-Bono
  • Rosalind Eeles
  • Colin S. Cooper
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Urologi och njurmedicin

Nyckelord

Originalspråkengelska
Sidor (från-till)1256-1269
TidskriftBJU International
Volym103
Utgåva nummer9
StatusPublished - 2009
PublikationskategoriForskning
Peer review utfördJa