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

Citation

Jhavar, S and Brewer, D and Edwards, S and Kote-Jarai, Z and Attard, G and Clark, J and Flohr, P and Christmas, T and Thompson, A and Parker, M and Shepherd, C and Stenman, UH and Marchbank, T and Playford, RJ and Woodhouse, C and Ogden, C and Fisher, C and Kovacs, G and Corbishley, C and Jameson, C and Norman, A and De-Bono, J and Bjartell, A and Eeles, R and Cooper, CS, Integration of ERG gene mapping and gene-expression profiling identifies distinct categories of human prostate cancer, B J U International: (British Journal of Urology), 103, (9) pp. 1256-1269. ISSN 1464-4096 (2009) [Refereed Article]

DOI: doi:10.1111/j.1464-410X.2008.08200.x

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 -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. © 2008 BJU International.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Genetics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Playford, RJ (Professor Ray Playford)
ID Code:72986
Year Published:2009
Web of Science® Times Cited:40
Deposited By:Research Division
Deposited On:2011-09-05
Last Modified:2011-09-05
Downloads:0

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