Integrative epigenetic taxonomy of primary prostate cancer

• DOI: 10.1038/s41467-018-07270-2
• Publication Date: 2018-11-15T10:49:51Z
• Authors: Suzan Stelloo; Ekaterina Nevedom...; Yongsoo Kim; Karianne Schuurman; Eider Valle-Encinas; João Lobo; Oscar Krijgsman; Daniel Simon Peeper; Seiwon Laura Chang; Felix Yi-Chung Feng; Lodewyk Frederik ...; Rui Henrique; Carmen Jerónimo; Andries Marinus B...; Wilbert Zwart
• Keywords: H3K4me3; Epigenomics

The Androgen Receptor (AR) is the key-driving transcription factor in prostate cancer, tightly controlled by epigenetic regulation. To date, most profiling has been performed cell lines or limited tissue samples. Here, to comprehensively study landscape, we perform RNA-seq with ChIP-seq for AR and histone modification marks (H3K27ac, H3K4me3, H3K27me3) 100 primary carcinomas. Integrative molecular subtyping of five data streams revealed three major subtypes which two were clearly TMPRSS2-ERG dictated. Importantly, identify a third subtype low chromatin binding activity AR, but high FGF WNT signaling. While positive neuroendocrine-hallmark genes, these tumors copy number-neutral mutational burden, significantly depleted genes characteristic poor-outcome associated luminal B-subtype. We present unique resource on transcriptional control revealing tight gene regulation differentially dictated over subtypes.