Print Email Facebook Twitter Integrative epigenetic taxonomy of primary prostate cancer Title Integrative epigenetic taxonomy of primary prostate cancer Author Stelloo, Suzan (Netherlands Cancer Institute) Nevedomskaya, Ekaterina (Netherlands Cancer Institute) Kim, Yongsoo (Netherlands Cancer Institute) Schuurman, Karianne (Netherlands Cancer Institute) Valle-Encinas, Eider (Netherlands Cancer Institute) Lobo, João (Universidade do Porto) Krijgsman, Oscar (Netherlands Cancer Institute) Peeper, Daniel Simon (Netherlands Cancer Institute) Chang, Seiwon Laura (University of California) Wessels, L.F.A. (TU Delft Pattern Recognition and Bioinformatics; Netherlands Cancer Institute) Date 2018 Abstract The Androgen Receptor (AR) is the key-driving transcription factor in prostate cancer, tightly controlled by epigenetic regulation. To date, most epigenetic profiling has been performed in cell lines or limited tissue samples. Here, to comprehensively study the epigenetic landscape, we perform RNA-seq with ChIP-seq for AR and histone modification marks (H3K27ac, H3K4me3, H3K27me3) in 100 primary prostate carcinomas. Integrative molecular subtyping of the five data streams revealed three major subtypes of which two were clearly TMPRSS2-ERG dictated. Importantly, we identify a third subtype with low chromatin binding and activity of AR, but with high activity of FGF and WNT signaling. While positive for neuroendocrine-hallmark genes, these tumors were copy number-neutral with low mutational burden, significantly depleted for genes characteristic of poor-outcome associated luminal B-subtype. We present a unique resource on transcriptional and epigenetic control in prostate cancer, revealing tight control of gene regulation differentially dictated by AR over three subtypes. To reference this document use: http://resolver.tudelft.nl/uuid:8638c4fb-4cd5-4f36-971a-237162050178 DOI https://doi.org/10.1038/s41467-018-07270-2 ISSN 2041-1723 Source Nature Communications, 9 (1), 1-12 Part of collection Institutional Repository Document type journal article Rights © 2018 Suzan Stelloo, Ekaterina Nevedomskaya, Yongsoo Kim, Karianne Schuurman, Eider Valle-Encinas, João Lobo, Oscar Krijgsman, Daniel Simon Peeper, Seiwon Laura Chang, L.F.A. Wessels, More Authors Files PDF s41467_018_07270_2.pdf 4.04 MB Close viewer /islandora/object/uuid:8638c4fb-4cd5-4f36-971a-237162050178/datastream/OBJ/view