Characterization of alternative promoter usage in advanced prostate cancer

In this study, we use deep whole genome transcriptome sequencing to show promoter activity changes during progression from normal prostate cells to advanced prostate disease. We show how androgen signaling and somatic alterations such as loss of the tumor suppressor RB1 or the activation of the ERG oncogene are linked to activity of transcription factors at noncanonical promoters. Alternative promoter usage analysis more accurately reflects changes in TF network during disease progression and in response to therapy. Lastly, we use matched whole genome methylation data to demonstrate a link between methylation and alternative promoter activity, dramatically improving the strength of association between gene expression and methylation data.EGA study EGAS00001006275