Abstract A26: Changes in gene expression in ERG-rearrangement positive prostate cancer are related to signaling, adhesion, and defense response
Authors: Massoner Petra , Kugler Karl , Klocker Helmut , Schäfer Georg , Müller Laurin , Bu Huajie , Kuner Ruprecht , Faelth Maria , Sültmann Holger , Rubin Mark A. , Graber Armin 
Published: May 2013

Since 2005 we know that around 50% of all prostate cancers harbor a genetic gene rearrangement. This gene rearrangement is formed by fusion of 5′ regulatory elements of an androgen-regulated gene to the coding region of a member of the E twenty-six (ETS) gene family of transcription factors. The major ETS transcription factor involved in the genetic rearrangement is the erythroblastosis virus E26 oncogene homolog gene (ERG). So far little is known about the cellular changes following ERG-rearrangement in prostate cancer.

We performed a meta-analysis on published gene expression data to identify ERG-rearrangement associated changes in gene expression. Six independent studies investigating 252 prostate cancer tissues were implemented in our analysis. ERG-rearrangement results in ERG overexpression. No information was available on the ERG-rearrangement status of the meta-analysis samples; thus we grouped the samples according to their ERG expression status. The comparative meta-analysis revealed 109 up-regulated and 58 down-regulated genes (fold-change &gt;1.5; corrected p-value &lt;0.1) in ERG-overexpressing compared to non ERG-overexpressing prostate cancers. The differentially regulated genes were related to the functional clusters signaling (extracellular signaling peptides and hormone signaling); adhesion (cell adhesion and extracellular matrix proteins) and defense response (wound healing and inflammatory response).

For meta-analysis validation we used data from an independent expression study performed on 57 prostate cancer tissues from the Innsbruck Prostate Cancer Biobank (independent patient cohort). In this study the ERG-rearrangement status was analyzed by fluorescent in situ hybridization. 76.6% of all genes found to be differentially regulated between ERG-rearrangement positive and ERG-rearrangement negative prostate cancers in the meta-analysis were verified in the validation study. The good overlap between the meta-analysis and the validation study demonstrates that our meta-analysis generated very stable results, which were independent of sample cohort, sample assignment and gene expression technology.

In summary we characterized changes in gene expression in ERG-rearrangement positive prostate cancer using published gene expression data. These data give new insights into the biology of prostate cancer. Furthermore our study demonstrates that published gene expression data are, beyond their initial scope, of great value to investigate new research questions.

Citation Format: Petra Massoner, Karl Kugler, Helmut Klocker, Georg Schäfer, Laurin Müller, Huajie Bu, Ruprecht Kuner, Maria Faelth, Holger Sültmann, Mark A. Rubin, Armin Graber. Changes in gene expression in ERG-rearrangement positive prostate cancer are related to signaling, adhesion, and defense response [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A26.