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

3 Citaties (Scopus)

Uittreksel

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.

TaalEngels
Aantal pagina's1
TijdschriftNature Communications
Volume9
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 21 nov 2018

Vingerafdruk

taxonomy
Androgen Receptors
Taxonomies
Epigenomics
Prostatic Neoplasms
Histone Code
cancer
genes
Genes
chromatin
gene expression
cultured cells
Gene expression
Histones
Chromatin
Tumors
Prostate
resources
Transcription Factors
tumors

Citeer dit

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). DOI: 10.1038/s41467-018-07270-2
Stelloo, Suzan ; Nevedomskaya, Ekaterina ; Kim, Yongsoo ; Schuurman, Karianne ; Valle-Encinas, Eider ; Lobo, João ; Krijgsman, Oscar ; Peeper, Daniel Simon ; Chang, Seiwon Laura ; Feng, Felix Yi Chung ; Wessels, Lodewyk Frederik Ary ; Henrique, Rui ; Jerónimo, Carmen ; Bergman, Andries Marinus ; Zwart, Wilbert. / Integrative epigenetic taxonomy of primary prostate cancer. In: Nature Communications. 2018 ; Vol. 9, Nr. 1.
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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.",
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Stelloo, S, Nevedomskaya, E, Kim, Y, Schuurman, K, Valle-Encinas, E, Lobo, J, Krijgsman, O, Peeper, DS, Chang, SL, Feng, FYC, Wessels, LFA, Henrique, R, Jerónimo, C, Bergman, AM & Zwart, W 2018, 'Integrative epigenetic taxonomy of primary prostate cancer' Nature Communications, vol. 9, nr. 1. DOI: 10.1038/s41467-018-07270-2

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

In: Nature Communications, Vol. 9, Nr. 1, 21.11.2018.

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

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AU - Stelloo,Suzan

AU - Nevedomskaya,Ekaterina

AU - Kim,Yongsoo

AU - Schuurman,Karianne

AU - Valle-Encinas,Eider

AU - Lobo,João

AU - Krijgsman,Oscar

AU - Peeper,Daniel Simon

AU - Chang,Seiwon Laura

AU - Feng,Felix Yi Chung

AU - Wessels,Lodewyk Frederik Ary

AU - Henrique,Rui

AU - Jerónimo,Carmen

AU - Bergman,Andries Marinus

AU - Zwart,Wilbert

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N2 - 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.

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Stelloo S, Nevedomskaya E, Kim Y, Schuurman K, Valle-Encinas E, Lobo J et al. Integrative epigenetic taxonomy of primary prostate cancer. Nature Communications. 2018 nov 21;9(1). Beschikbaar vanaf, DOI: 10.1038/s41467-018-07270-2