Integration of ERG gene mapping and gene-expression profiling identifies distinct categories of human prostate cancer.
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.
Jhavar
Sameer
S
Institute of Cancer Research, Male Urological Cancer Research Centre, Sutton, Surrey, UK.
Brewer
Daniel
D
Edwards
Sandra
S
Kote-Jarai
Zsofia
Z
Attard
Gerhardt
G
Clark
Jeremy
J
Flohr
Penny
P
Christmas
Timothy
T
Thompson
Alan
A
Parker
Matthew
M
Shepherd
Christopher
C
Stenman
Ulf-Hakan
UH
Marchbank
Tania
T
Playford
Raymond J
RJ
Woodhouse
Christopher
C
Ogden
Christopher
C
Fisher
Cyril
C
Kovacs
Gyula
G
Corbishley
Cathy
C
Jameson
Charles
C
Norman
Andy
A
De-Bono
Johann
J
Bjartell
Anders
A
Eeles
Rosalind
R
Cooper
Colin S
CS
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
D002352:Carrier Proteins; C072312:ERG protein, human; C486642:SPINK1 protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014359:Trypsin Inhibitor, Kazal Pancreatic