Scaffold Attachment Factor B1: A Novel Chromatin Regulator of Prostate Cancer Metabolism
Technical Report,01 Aug 2014,31 Jul 2015
Cedar-Sinai Medical Center Los Angeles United States
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Progress was made in four major areas of study in the first year of the funding period. First, I determined the overlapping target genes of SAFB1 and AR. Second, I identified a SAFB1-dependent gene signature in clinical specimens using a large prostate cancer transcriptome dataset I assembled. Interestingly, the enriched cellular processes were associated with aggressive cancer behavior, including steroid hormone response, blood vessel formation, and RNA processing. Third, I found I could classify prostate cancer subtypes into three distinct categories, using only transcriptome data. One of these subtypes is functionally not possible to characterize, based on currently published profiling and genomic analyses. Fourth, I searched for possible regulators of this newly identified subtype using an integrative network analysis of hundreds of castration-resistant PC RNA expression profiles. This analysis revealed a set of key transcription factors TFs that appear to play a major role in metastatic castration-resistant prostate cancer mCRPC. Among these TFs, we identified ONECUT2, which appears to be a master regulator of the novel prostate cancer subtype in our classification scheme.