Integrative epigenetic taxonomy of primary prostate cancer

Suzan Stelloo, Ekaterina Nevedomskaya, Yongsoo Kim, Karianne Schuurman, Eider Valle-Encinas, João Lobo, Oscar Krijgsman, Daniel Simon Peeper, Seiwon Laura Chang, Felix Yi Chung Feng, Lodewyk Frederik Ary Wessels, Rui Henrique, Carmen Jerónimo, Andries Marinus Bergman, Wilbert Zwart

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

103 Citaten (Scopus)
213 Downloads (Pure)

Samenvatting

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.

Originele taal-2Engels
Artikelnummer4900
Aantal pagina's1
TijdschriftNature Communications
Volume9
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 1 dec. 2018

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