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

Jhavar, Sameer; Brewer, Daniel; Edwards, Sandra; Kote-Jarai, Zsofia; Attard, Gerhardt; Clark, Jeremy; Flohr, Penny; Christmas, Timothy; Thompson, Alan and Parker, Matthew, et al. (2009) In BJU International1999-01-01+01:00 103(9). p.1256-1269
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... (More)
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. (Less)
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publication status
published
subject
keywords
expression microarray, SPINK1, ERG fusion, prostate cancer
in
BJU International1999-01-01+01:00
volume
103
issue
9
pages
1256 - 1269
publisher
Blackwell Science Ltd
external identifiers
  • wos:000265424300021
  • scopus:64249128160
ISSN
1464-4096
DOI
10.1111/j.1464-410X.2008.08200.x
language
English
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yes
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575ce562-116c-4e53-8b0c-69efd6096b0a (old id 1428058)
date added to LUP
2009-06-25 11:56:50
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2017-08-06 03:38:42
@article{575ce562-116c-4e53-8b0c-69efd6096b0a,
  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.},
  author       = {Jhavar, Sameer and Brewer, Daniel and Edwards, Sandra and Kote-Jarai, Zsofia and Attard, Gerhardt and Clark, Jeremy and Flohr, Penny and Christmas, Timothy and Thompson, Alan and Parker, Matthew and Shepherd, Christopher and Stenman, Ulf-Hakan and Marchbank, Tania and Playford, Raymond J. and Woodhouse, Christopher and Ogden, Christopher and Fisher, Cyril and Kovacs, Gyula and Corbishley, Cathy and Jameson, Charles and Norman, Andy and De-Bono, Johann and Bjartell, Anders and Eeles, Rosalind and Cooper, Colin S.},
  issn         = {1464-4096},
  keyword      = {expression microarray,SPINK1,ERG fusion,prostate cancer},
  language     = {eng},
  number       = {9},
  pages        = {1256--1269},
  publisher    = {Blackwell Science Ltd},
  series       = {BJU International1999-01-01+01:00},
  title        = {Integration of ERG gene mapping and gene-expression profiling identifies distinct categories of human prostate cancer},
  url          = {http://dx.doi.org/10.1111/j.1464-410X.2008.08200.x},
  volume       = {103},
  year         = {2009},
}