ArticleNature genetics2020
The DNA methylation landscape of advanced prostate cancer.
Open access · bronzeAbstract readMulticenter Study
In one paragraph
Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
235citing papers in PubMed, 1 pooled it
16.5field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
235 citing papers in PubMed, 1 synthesis or guideline pooled it, 343 citations in OpenAlex.
- Advances in sequencing and omics studies in prostate cancer: unveiling molecular pathogenesis and clinical applications.Frontiers in oncology · 2024Pooled it
- Non-conventional histologies of prostate cancer: from morphology to biology-driven precision oncology.The oncologist · 2026Review
- Spatial and Epigenetic Polarity of the AR Promoter During Prostate Cancer Progression: An In Silico Analysis.International journal of molecular sciences · 2026Article
- Combined BET bromodomain and DNA methyltransferase inhibition targets critical survival pathways in transdifferentiated prostate cancer.JCI insight · 2026Article
- ATP-dependent chromatin remodelers in prostate cancer progression and therapeutic resistance.Endocrinology · 2026Review
- Bioengineered systems to exploit tumor microenvironment metabolism.Trends in cancer · 2026Review
- TET2 as a Context-Dependent Epigenetic Integrator in Clonal Hematopoiesis, Inflammation, Cancer, and Immunotherapy.Cell biochemistry and function · 2026Review
- Systematic analysis of hippo pathway signaling identifies TEAD1 as a transcriptional regulator of neuroendocrine prostate cancer.Neoplasia (New York, N.Y.) · 2026Article
- Towards implementation of precision medicine biomarkers in early detection and prognostication of prostate cancer.Cancer metastasis reviews · 2026Review
- Long-read sequencing of single cell-derived melanoma sublines reveals divergent and parallel genomic and epigenomic evolutionary trajectories.Nature communications · 2026Article
- Genome-wide methylome profiling of cell-free DNA enables prognostication of patients with castration-resistant prostate cancer.British journal of cancer · 2026Article
- NNMT Loss Drives Cancer Progression by enhancing SAM availability for mTORC1 Signaling and Chromatin Methylation.bioRxiv : the preprint server for biology · 2026Article
- Epigenetic modulation of prostate cancer disparities in men with African ancestry.Nature reviews. Urology · 2026Review
- Review
- DDX5 (p68) and UbE2T as emerging superior cancer therapeutic targets: dual molecular glue target degradation by FL118 for conquering difficult-to-treat cancers.Journal of experimental & clinical cancer research : CR · 2026Review
- Epigenetic regulation in a high-sugar environment (Review).International journal of molecular medicine · 2026Review
- Development and validation of a 5mC-based prognostic model for lung adenocarcinoma survival.Cell reports. Medicine · 2026Article
- Artificial Intelligence Design for Race-Based Prostate Cancer Stage Classification With Multilayer Perceptron: Feature Selection Optimization Approach.JMIR formative research · 2026Article
- Landscape of Allele-Specific Expression in Prostate Cancer Reveals Recurrent, Stage-Specific Events in AR Signaling and Resistance Pathways.Molecular cancer research : MCR · 2026Article
- Phase I multi-center clinical and biomarker study of the dual-action androgen receptor inhibitor ONCT-534.Investigational new drugs · 2026Article
175 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
69 authors at 20 institutions in 4 countries.
Shuang G Zhao *Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
William S Chen *Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Haolong Li *Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Adam FoyeHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Meng ZhangDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Martin SjöströmDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2629-9966
Rahul AggarwalHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Denise PlaydleHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Arnold LiaoIllumina Inc., San Diego, CA, USA.
Joshi J AlumkalKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Rajdeep DasDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1041-4931
Jonathan ChouDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Junjie T HuaPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Travis J BarnardDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Adina M BaileyHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Eric D ChowDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8079-918X
Marc D PerryDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6476-2942
Ha X DangMcDonnell Genome Institute, Washington University, St. Louis, MO, USA.
Rendong YangThe Hormel Institute, University of Minnesota, Austin, MN, USA.ORCID http://orcid.org/0000-0002-9512-2240
Ruhollah Moussavi-BaygiDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Li ZhangHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Mohammed AlshalalfaDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
S Laura ChangDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Kathleen E HoulahanOntario Institute for Cancer Research, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0002-2273-2099
Yu-Jia ShiahOntario Institute for Cancer Research, Toronto, Ontario, Canada.
Tomasz M BeerKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
George ThomasKnight Cancer Institute, Oregon Health & Science University, Portland, OR, USA.
Kim N ChiVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Martin GleaveVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Amina ZoubeidiVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Robert E ReiterJonsson Comprehensive Cancer Center, Departments of Medicine and Urology, University of California Los Angeles, Los Angeles, CA, USA.
Matthew B RettigJonsson Comprehensive Cancer Center, Departments of Medicine and Urology, University of California Los Angeles, Los Angeles, CA, USA.
Owen WitteDepartment of Microbiology, Immunology, and Molecular Genetics at the David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
M Yvonne KimDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Lawrence FongHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Daniel E SprattDepartment of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
Todd M MorganRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0002-1140-0603
Rohit BoseHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6785-0697
Franklin W HuangHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Hui LiDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Lisa ChesnerDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA.
Tanushree ShenoyHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Hani GoodarziDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9648-8949
Irfan A AsanganiDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, PA, USA.
Shahneen SandhuPeter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.
Joshua M LangDepartment of Medicine, University of Wisconsin, Madison, WI, USA.
Nupam P MahajanSiteman Cancer Center, Washington University, St. Louis, MO, USA.
Primo N LaraDivision of Hematology Oncology, Department of Internal Medicine, University of California Davis, Sacramento, CA, USA.
Christopher P EvansComprehensive Cancer Center, University of California Davis, Sacramento, CA, USA.
Phillip FebboIllumina Inc., San Diego, CA, USA.
Serafim BatzoglouIllumina Inc., San Diego, CA, USA.
Karen E KnudsenDepartment of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Housheng H HePrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-2898-3363
Jiaoti HuangDepartment of Pathology, Duke University, Durham, NC, USA.
Wilbert ZwartNetherlands Cancer Institute, Oncode Institute, Amsterdam, the Netherlands.
Joseph F CostelloDepartment of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Jianhua LuoDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
Scott A TomlinsMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Alexander W WyattVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Scott M DehmMasonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.ORCID http://orcid.org/0000-0002-7827-5579
Alan AshworthHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
Luke A GilbertHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5854-0825
Paul C BoutrosDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0003-0553-7520
Kyle FarhIllumina Inc., San Diego, CA, USA.ORCID http://orcid.org/0000-0001-6947-8537
Arul M ChinnaiyanRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-8743-7480
Christopher A MaherMcDonnell Genome Institute, Washington University, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-9035-603X
Eric J SmallHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3191-6268
David A QuigleyHelen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-4726-1473
Felix Y FengDepartment of Radiation Oncology, University of California San Francisco, San Francisco, CA, USA. Felix.Feng@ucsf.edu.ORCID http://orcid.org/0000-0002-0963-7687
University of California, San Francisco · USIllumina (United States) · USUniversity of California, Los Angeles · USOregon Health & Science University · USUniversity of British Columbia · CAUniversity of Michigan · USJames S. McDonnell Foundation · USOntario Institute for Cancer Research · CAUniversity Health Network · CAUniversity of California, Davis · USUniversity of Minnesota · USBC Cancer Agency · CADuke University · USHoward Hughes Medical Institute · USThe Netherlands Cancer Institute · NLThe University of Melbourne · AUThomas Jefferson University · USUniversity of Pennsylvania · USUniversity of Pittsburgh · USUniversity of Wisconsin–Madison · US
Funding
NRG Oncology Network Group Operations Center - GY9 BIQSFP Reports/BudgetsU10CA180868 · NCI · NRG ONCOLOGY FOUNDATION, INC. · PI NORMAN WOLMARK · 2014 to 2026
$206.8MWomen's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5MStaff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Laura Marcu · 2002 to 2026
$84.9MUCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FREEMAN, MICHAEL R · 2002 to 2023
$42.6MTissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Robert Timothy Dess · 2014 to 2026
$27.6MUCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI David A. Nathanson · 2017 to 2026
$25.2MStrategic Vision & Impact on Environmental HealthP30ES017885 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Dana Dolinoy · 2011 to 2026
$21.3MExploring Precision Oncology: From Gene Fusions to lncRNAsR35CA231996 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M · 2018 to 2024
$6.4MAR Gene Rearrangements and AR Signaling in Prostate CancerR01CA174777 · NCI · UNIVERSITY OF MINNESOTA · PI Scott M. Dehm · 2013 to 2026
$4.9MBiomarker Approaches to Individualizing Systemic Therapy for High Risk Prostate CancerR01CA240582 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FENG, FELIX YI-CHUNG, NGUYEN, PAUL L · 2020 to 2024
$3.4MDiscovery and qualification of transcriptomic biomarkers for the early detection of aggressive prostate cancerU01CA214170 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M · 2016 to 2021
$3.3MMolecular Mechanisms of Castration Resistant Prostate Cancer Recurrence & Therapeutic StrategiesR01CA227025 · NCI · WASHINGTON UNIVERSITY · PI FENG, FELIX YI-CHUNG, MAHAJAN, NUPAM P · 2019 to 2023
$2.8MHoward Hughes Medical InstituteNCI NIH HHS DP2 CA239597NCI NIH HHS K99 CA204602NCI NIH HHS P30 CA016042NCI NIH HHS P30 CA093373NCI NIH HHS P50 CA092131NCI NIH HHS P50 CA186786NCI NIH HHS P50 CA211015NCI NIH HHS R00 CA204602NCI NIH HHS R01 CA174777NCI NIH HHS R01 CA208258NCI NIH HHS R01 CA227025NCI NIH HHS R01 CA230516NCI NIH HHS R01 CA240582NCI NIH HHS R35 CA231996NCI NIH HHS U01 CA214170NCI NIH HHS U01 CA214194NCI NIH HHS U10 CA180868NIEHS NIH HHS P30 ES017885
Abstract
Although DNA methylation is a key regulator of gene expression, the comprehensive methylation landscape of metastatic cancer has never been defined. Through whole-genome bisulfite sequencing paired with deep whole-genome and transcriptome sequencing of 100 castration-resistant prostate metastases, we discovered alterations affecting driver genes that were detectable only with integrated whole-genome approaches. Notably, we observed that 22% of tumors exhibited a novel epigenomic subtype associated with hypermethylation and somatic mutations in TET2, DNMT3B, IDH1 and BRAF. We also identified intergenic regions where methylation is associated with RNA expression of the oncogenic driver genes AR, MYC and ERG. Finally, we showed that differential methylation during progression preferentially occurs at somatic mutational hotspots and putative regulatory regions. This study is a large integrated study of whole-genome, whole-methylome and whole-transcriptome sequencing in metastatic cancer that provides a comprehensive overview of the important regulatory role of methylation in metastatic castration-resistant prostate cancer.
Indexed as
AgedAged, 80 and overCarcinogenesisDNA MethylationEpigenomicsExome SequencingGene Expression Regulation, NeoplasticGenomeHumansMaleMiddle AgedMutationProspective StudiesProstatic NeoplasmsSequence Analysis, DNAWhole Genome Sequencing
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