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 () and Wilbert Zwart ()
Additional contact information
Suzan Stelloo: The Netherlands Cancer Institute
Ekaterina Nevedomskaya: The Netherlands Cancer Institute
Yongsoo Kim: The Netherlands Cancer Institute
Karianne Schuurman: The Netherlands Cancer Institute
Eider Valle-Encinas: The Netherlands Cancer Institute
João Lobo: Research Center of the Portuguese Oncology Institute-Porto
Oscar Krijgsman: The Netherlands Cancer Institute
Daniel Simon Peeper: The Netherlands Cancer Institute
Seiwon Laura Chang: University of California San Francisco (UCSF)
Felix Yi-Chung Feng: University of California San Francisco (UCSF)
Lodewyk Frederik Ary Wessels: The Netherlands Cancer Institute
Rui Henrique: Research Center of the Portuguese Oncology Institute-Porto
Carmen Jerónimo: Research Center of the Portuguese Oncology Institute-Porto
Andries Marinus Bergman: The Netherlands Cancer Institute
Wilbert Zwart: The Netherlands Cancer Institute

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07270-2

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DOI: 10.1038/s41467-018-07270-2

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