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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number4900
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

Cite this

Stelloo, S., Nevedomskaya, E., Kim, Y., Schuurman, K., Valle-Encinas, E., Lobo, J., ... Zwart, W. (2018). Integrative epigenetic taxonomy of primary prostate cancer. Nature Communications, 9(1), [4900]. https://doi.org/10.1038/s41467-018-07270-2