Integrative epigenetic taxonomy of primary prostate cancer
Open accessAbstract
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 claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Integration of ATAC-seq data with AR ChIP-seq data demonstrated that more than 80% of differentially accessible ATAC-seq peaks overlapped with AR ChIP-seq peaks.
“Integration of our ATAC-seq data with AR ChIP–seq data52 demonstrated that more than 80% of the differentially accessible ATAC-seq peaks overlapped with AR ChIP–seq peaks (Fig. 5j).”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [52]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 53 · Cited by 154
Research works printed but not linked: 1
- [50]Shao, W., He, L. & Yu, P. S. Multiple Incomplete Views Clustering via Weighted Nonnegative Matrix Factorization with L2,1Regularization, Vol. 9284 (Springer, 2015).
- Authors
- 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.
- Affiliations
- The Netherlands Cancer Institute (NL)
- Universidade do Porto (PT)
- University of California, San Francisco (US)
- Corresponding author
- Bergman, Andries Marinus
- Zwart, Wilbert
- ORCID
- Venue
- Nature Communications
- Published
- 2018-11-21
- Volume
- 9
- Issue
- 1
- Pages
- 4900-4900
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6249266
- OpenAlex
- W2900864487
- Cited by
- 154
- References
- 53
- Citations by year
- 2026: 12 · 2025: 22 · 2024: 20 · 2023: 18 · 2022: 29 · 2021: 23 · 2020: 18 · 2019: 12
- FWCI
- 9.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- TU/e Research Portal (publishedVersion, other-oa)
- TU/e Research Portal (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Repository (Delft University of Technology) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- TU/e Research Portal (submittedVersion, other-oa)
- Funders
- Movember Foundation (NKI01)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (016.156.401)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- primary prostate cancer, androgen receptor, epigenetic regulation, histone modifications, H3K27ac, H3K4me3, H3K27me3, molecular subtyping, TMPRSS2-ERG fusion, FGF signaling, Wnt signaling, neuroendocrine prostate cancer, luminal B, chromatin binding, copy number alterations, mutational burden
- MeSH terms
- Aged, Carcinoma, Histones, Humans, Male, Middle Aged, Prostatic Neoplasms, Receptors, Androgen, Sequence Analysis, RNA, Epigenesis, Genetic, Epigenomics, Molecular Typing
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
