• Genome-wide germline correlates of the epigenetic landscape of prostate cancer

      Houlahan, KE; Shiah, YJ; Gusev, A; Yuan, J; Ahmed, M; Shetty, A; Ramanand, SG; Yao, CQ; Bell, C; O'Connor, E; et al. (2019)
    • Widespread and functional RNA circularization in localized prostate cancer

      Chen, S; Huang, V; Xu, X; Livingstone, J; Soares, F; Jeon, J; Zeng, Y; Hua, JT; Petricca, J; Guo, H; et al. (2019)
      The cancer transcriptome is remarkably complex, including low-abundance transcripts, many not polyadenylated. To fully characterize the transcriptome of localized prostate cancer, we performed ultra-deep total RNA-seq on 144 tumors with rich clinical annotation. This revealed a linear transcriptomic subtype associated with the aggressive intraductal carcinoma sub-histology and a fusion profile that differentiates localized from metastatic disease. Analysis of back-splicing events showed widespread RNA circularization, with the average tumor expressing 7,232 circular RNAs (circRNAs). The degree of circRNA production was correlated to disease progression in multiple patient cohorts. Loss-of-function screening identified 11.3% of highly abundant circRNAs as essential for cell proliferation; for ?90% of these, their parental linear transcripts were not essential. Individual circRNAs can have distinct functions, with circCSNK1G3 promoting cell growth by interacting with miR-181. These data advocate for adoption of ultra-deep RNA-seq without poly-A selection to interrogate both linear and circular transcriptomes.