Abstract LB-21: Emergence of castration resistant prostate cancer class defined by recurrentERGfusion

The role of recurrent ETS gene fusions in castration resistant prostate cancer (CRPC) is poorly understood. We characterized the transcriptome of CRPC by interrogating a cohort of 54 men with locally advanced or metastatic CRPC using a gene expression profiling method recently established for formalin-fixed paraffin-embedded tissue. We found increased expression of multiple genes in ERG rearranged tumors which suggests a selective growth advantage under oxygen poor conditions. We discovered that trefoil factor 3 (TFF3) is the top differentially regulated gene by both ERG rearrangement and resistance to therapy. Conventional chromatin immunoprecipitation (ChIP)-PCR and ChIP-seq data revealed direct binding of ERG to ETS binding sites in the TFF3 promoter in ERG rearranged prostate cancer cell lines, which was confirmed in ERG rearranged hormone naive prostate cancer (HNPC) and CRPC tissue samples. In vitro data suggested that ERG has an inhibitory effect on TFF3 expression in hormone naive cancer, which was relieved in CRPC depending on the level of AR expression. These findings reveal an interplay between ERG rearrangement and AR signaling in CRPC, and provide perspective towards novel therapeutic targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-21.