Published online before print December 28, 2007

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Journal of Molecular Diagnostics 2008, Vol. 10, No. 1
Copyright © 2008 American Society for Investigative Pathology & Association for Molecular Pathology
DOI: 10.2353/jmoldx.2008.070085

Technical Advance

Detection of TMPRSS2-ERG Translocations in Human Prostate Cancer by Expression Profiling Using GeneChip Human Exon 1.0 ST Arrays

Sameer Jhavar^*, Alison Reid^*, Jeremy Clark^*, Zsofia Kote-Jarai^*, Timothy Christmas, Alan Thompson, Christopher Woodhouse, Christopher Ogden, Cyril Fisher, Cathy Corbishley^¶, Johann De-Bono, Rosalind Eeles^*, Daniel Brewer^* and Colin Cooper^*

From the Institute of Cancer Research, *Male Urological Cancer Research Centre, Sutton, Surrey; the Royal Marsden NHS Trust Foundation Hospital, Sutton, Surrey; the Departments of Academic Urology and Histopathology, the Royal Marsden NHS Foundation Trust, London; and the Department of Cellular Pathology, ^¶the St. Georges Hospital NHS Foundation Trust, London, United Kingdom

Abstract

Translocation of TMPRSS2 to the ERG gene, found in a high proportion of human prostate cancer, results in overexpression of the 3'-ERG sequences joined to the 5'-TMPRSS2 promoter. The studies presented here were designed to test the ability of expression analysis on GeneChip Human Exon 1.0 ST arrays to detect 5'-TMPRSS2-ERG-3' hybrid transcripts encoded by this translocation. Monitoring the relative expression of each ERG exon revealed altered transcription of the ERG gene in 15 of a series of 27 prostate cancer samples. In all cases, exons 4 to 11 exhibited enhanced expression compared with exons 2 and 3. This pattern of expression indicated that the most abundant hybrid transcripts involve fusions to ERG exon 4, and RT-PCR analyses confirmed the joining of TMPRSS2 exon 1 to ERG exon 4 in all 15 cases. The exon expression patterns also indicated that TMPRSS2-ERG fusion transcripts commonly contain deletion of ERG exon 8. Analysis of gene-level data from the arrays allowed the identification of genes whose expression levels significantly correlated with the presence of the translocation. These studies demonstrate that expression analyses using exon arrays represent a valuable approach for detecting ETS gene translocation in prostate cancer, in parallel with analyses of gene expression profiles.

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