Prostate cancer is the second most prevalent malignancy in men. Biomarkers for outcome prediction are urgently needed, so that high-risk patients could be monitored more closely postoperatively. To identify prognostic markers and to determine causal players in prostate cancer progression, we assessed changes in chromatin state during tumor development and progression. Based on this, we assessed genomewide androgen receptor/chromatin binding and identified a distinct androgen receptor/chromatin binding profile between primary prostate cancers and tumors with an acquired resistance to therapy. These differential androgen receptor/chromatin interactions dictated expression of a distinct gene signature with strong prognostic potential. Further refinement of the signature provided us with a concise list of nine genes that hallmark prostate cancer outcome in multiple independent validation series. In this report, we identified a novel gene expression signature for prostate cancer outcome through generation of multilevel genomic data on chromatin accessibility and transcriptional regulation and integration with publically available transcriptomic and clinical datastreams. By combining existing technologies, we propose a novel pipeline for biomarker discovery that is easily implementable in other fields of oncology.

Androgen receptor profiling, ChIP-seq, Companion diagnostics for prostate cancer, FAIRE-seq, Treatment prediction
dx.doi.org/10.15252/emmm.201505424, hdl.handle.net/1765/83490
EMBO Molecular Medicine
Department of Urology

Stelloo, S, Nevedomskaya, E, van der Poel, H.G, de Jong, J, Leenders, G.J.H.L, Jenster, G.W, … Zwart, W. (2015). Androgen receptor profiling predicts prostate cancer outcome. EMBO Molecular Medicine, 7(11), 1450–1464. doi:10.15252/emmm.201505424