Use of alternative promoters by oncogene transcription factors increases as prostate tumours progress from benign to metastatic castration-resistant disease. This observation indicates that alternative promoter use intensifies the transcriptional effects of tumour-driving genes in prostate cancer.

Deep RNA-sequencing analysis of 274 biopsy samples of benign prostate tissue, localized prostate tumours and metastatic castration-resistant prostate cancer (mCRPC) showed that genes upregulated in localized prostate cancer or mCRPC and known oncogenes were at an increased likelihood of switching from a single alternative promoter to multiple ones in tumours. The opposite effect was observed for downregulated genes. Increased alternative promoter use was associated with upregulation of genes relevant to prostate cancer progression.