Integrative epigenetic taxonomy of primary prostate cancer
| Autor: | Andries M. Bergman, Eider Valle-Encinas, Seiwon Laura Chang, Karianne Schuurman, João Lobo, Rui Henrique, Felix Y. Feng, Carmen Jerónimo, Suzan Stelloo, Wilbert Zwart, Ekaterina Nevedomskaya, Oscar Krijgsman, Daniel S. Peeper, L. F. A. Wessels, Yongsoo Kim |
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| Přispěvatelé: | Pathology, Internal medicine, Institute for Complex Molecular Systems, Chemical Biology |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Epigenomics Male Androgen/metabolism Science Histones/metabolism General Physics and Astronomy Receptors Androgen/metabolism Biology SDG 3 – Goede gezondheid en welzijn General Biochemistry Genetics and Molecular Biology Article Carcinoma/metabolism Epigenesis Genetic Histones 03 medical and health sciences Prostate cancer Genetic SDG 3 - Good Health and Well-being Receptors medicine Humans Epigenetics lcsh:Science Aged Regulation of gene expression Multidisciplinary Sequence Analysis RNA Chromatin binding Carcinoma Wnt signaling pathway Prostatic Neoplasms General Chemistry Middle Aged Prostatic Neoplasms/metabolism medicine.disease 3. Good health Androgen receptor Molecular Typing 030104 developmental biology Receptors Androgen Cancer research H3K4me3 RNA lcsh:Q Sequence Analysis Epigenesis |
| Zdroj: | Nature Communications, Vol 9, Iss 1, Pp 1-12 (2018) Nature Communications, 9(1):4900. Nature Publishing Group UK Nature Communications, 9(1) Nature Communications, 9(1):4900. Nature Publishing Group Nature Communications Stelloo, S, Nevedomskaya, E, Kim, Y, Schuurman, K, Valle-Encinas, E, Lobo, J, Krijgsman, O, Peeper, D S, Chang, S L, Feng, F Y C, Wessels, L F A, Henrique, R, Jerónimo, C, Bergman, A M & Zwart, W 2018, ' Integrative epigenetic taxonomy of primary prostate cancer ', Nature Communications, vol. 9, no. 1, 4900 . https://doi.org/10.1038/s41467-018-07270-2 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-018-07270-2 |
| Popis: | 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. The Androgen Receptor (AR) is the main driver of prostate cancer and functions in conjunction with chromatin modifications. Here, the authors comprehensively profile 100 primary prostate carcinomas by sequencing RNA transcripts in combination with ChIP-sequencing for AR and the active histone marks H3K27ac, H3K4me3 and repressive mark H3K27me3. |
| Databáze: | OpenAIRE |
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