Transcriptional landscape of PTEN loss in primary prostate cancer

Abstract

ABSTRACTPTEN is the most frequently lost tumor suppressor in primary prostate cancer (PCa) and its loss is associated with aggressive disease. However, the transcriptional changes associated with PTEN loss in PCa have not been described in detail. Here, we applied a meta-analysis approach, leveraging two large PCa cohorts with experimentally validated PTEN and ERG status, to derive a transcriptomic signature ofPTENloss, while also accounting for potential confounders due toERGrearrangements. Strikingly, the signature indicates a strong activation of both innate and adaptive immune systems uponPTENloss, as well as an expected activation of cell-cycle genes. Moreover, we made use of our recently developed FC-R2 expression atlas to expand this signature to include many non-coding RNAs recently annotated by the FANTOM consortium. With this resource, we analyzed the TCGA-PRAD cohort, creating a comprehensive transcriptomic landscape ofPTENloss in PCa that comprises both the coding and an extensive non-coding counterpart.