ArticleCancer research2022
The 5-Hydroxymethylcytosine Landscape of Prostate Cancer.
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Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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52citing papers in PubMed
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Who cites it
52 citing papers in PubMed, 62 citations in OpenAlex.
- ctDNA and tumor-based biomarkers of giredestrant response in acelERA breast cancer.Nature communications · 2026Trial
- DNA Methylation as a Programmable Information Layer: From Molecular Marks to Disease State Engineering.International journal of molecular sciences · 2026Review
- Urinary DNA Methylation and Hydroxymethylation Dynamics as Candidate Biomarkers of Occupational Chemical Exposure-An Exploratory Pilot Study.International journal of molecular sciences · 2026Article
- Relationship between Prostate Cancer and Benign Hyperplasia: Role of Inflammation-Induced Oxidative Stress, Vitamin C, and Epigenetics.The world journal of men's health · 2026Review
- Combined epigenomic landscapes of 5mC, 5hmC, and 6mA modifications in papillary thyroid carcinogenesis.Communications biology · 2026Article
- Inflammatory and Epigenetic Biomarkers in Prostate Disease: Current Evidence, Clinical Limitations, and Future Multimarker Strategies.Diagnostics (Basel, Switzerland) · 2026Review
- Circulating cell-free methylated DNA immunoprecipitation sequencing (cfMeDIP-seq) in oncology: from technological advances to clinical applications.NPJ precision oncology · 2026Review
- Exploring the Utility of Cell-Free DNA Hydroxymethylation Profiling in Small-Cell Lung Cancer.International journal of molecular sciences · 2026Article
- Integrative Whole-Genome and Epigenome Profiling of cfDNA in Familial Prostate Cancer: Insights from a Pilot Study.Biomedicines · 2026Article
- Liquid biopsy epigenetics: establishing a molecular profile based on cell-free DNA.Molecular oncology · 2026Review
- Integrative dual ctDNA 5mC/5hmC methylomics and clonal reconstruction infer tumor transcription and resistance phenotypes in metastatic prostate cancer.Research square · 2026Article
- Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer.Journal of the National Cancer Center · 2026Review
- Single-cell and spatial omics of metabolic-immune ecosystems in prostate cancer: from androgen signaling to therapy resistance.Frontiers in immunology · 2026Review
- 5mC and 5hmC methylation sequencing: the power of 6-base sequencing in a multiomic era.Epigenomics · 2026Review
- Vitamin C enhances cisplatin sensitivity in bladder cancer via 5hmC-mediated epigenetic modulation of ATF4.Clinical epigenetics · 2025Article
- Aging of the human eye lens: Epigenetic landscape and therapeutic targets in age‑related cataracts (Review).International journal of molecular medicine · 2025Review
- 5-hydroxymethylcytosine analysis reveals stable epigenomic changes in tumor tissue that enable cancer detection in cell-free DNA.Communications biology · 2025Article
- Histologic Transformation in Cancer: The Path for Clinical Translation.Cancer discovery · 2025Review
- Prostate cancer epigenetics - from pathophysiology to clinical application.Nature reviews. Urology · 2025Review
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
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Authors and funding
64 authors at 20 institutions in 7 countries.
Martin Sjöström *Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-2629-9966
Shuang G Zhao *Department of Human Oncology, University of Wisconsin-Madison, Madison, WI.
Samuel Levy *Bluestar Genomics Inc., San Diego, CA.ORCID 0000-0002-4444-5103
Meng Zhang *Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0003-1042-6294
Yuhong NingBluestar Genomics Inc., San Diego, CA.
Raunak ShresthaHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-1144-1413
Arian LundbergHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-6630-2787
Cameron HerbertsVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-9929-8374
Adam FoyeHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-9910-9836
Rahul AggarwalHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0001-7003-7982
Junjie T HuaHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-1197-1174
Haolong LiHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
Anna BergamaschiBluestar Genomics Inc., San Diego, CA.ORCID 0000-0001-8709-1766
Corinne Maurice-DrorVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0003-4455-4497
Ashutosh MaheshwariHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
Sujun ChenDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Sarah W S NgVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-7647-6940
Wenbin YeDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0002-9303-9363
Jessica PetriccaDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Michael FraserPrincess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Lisa ChesnerHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
Marc D PerryHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0001-6476-2942
Thaidy Moreno-RodriguezHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0003-3588-3889
William S ChenHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
Joshi J AlumkalDivision of Hematology and Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI.ORCID 0000-0003-1278-0166
Jonathan ChouHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0003-1258-0391
Alicia K MorgansDana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Tomasz M BeerKnight Cancer Institute, Oregon Health and Science University, Portland, OR.ORCID 0000-0001-5600-9993
George V ThomasKnight Cancer Institute, Oregon Health and Science University, Portland, OR.
Martin GleaveVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
Paul LloydBluestar Genomics Inc., San Diego, CA.ORCID 0000-0003-3508-5553
Tierney PhillipsBluestar Genomics Inc., San Diego, CA.
Erin McCarthyBluestar Genomics Inc., San Diego, CA.ORCID 0000-0002-3845-4142
Michael C HaffnerDivisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA.ORCID 0000-0003-0809-6425
Amina ZoubeidiVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-0498-142X
Matti AnnalaVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.
Robert E ReiterDepartments of Medicine, Hematology/Oncology and Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.ORCID 0000-0002-7962-3985
Matthew B RettigDepartments of Medicine, Hematology/Oncology and Urology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.ORCID 0000-0002-7394-3056
Owen N WitteDepartment of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA.ORCID 0000-0003-4461-4533
Lawrence FongHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-6428-428X
Rohit BoseHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-6785-0697
Franklin W HuangHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
Jianhua LuoDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA.ORCID 0000-0002-0943-8872
Anders BjartellDepartment of Translational Medicine, Medical Faculty, Lund University, Malmö, Sweden.
Joshua M LangDepartment of Medicine, University of Wisconsin-Madison, Madison, WI.ORCID 0000-0002-0943-8872
Nupam P MahajanSiteman Cancer Center, Washington University, St. Louis, MO.ORCID 0000-0002-4150-602X
Primo N LaraDivision of Hematology Oncology, Department of Internal Medicine, University of California Davis, Sacramento, CA.
Christopher P EvansComprehensive Cancer Center, University of California Davis, Sacramento, CA.ORCID 0000-0001-5626-8901
Phuoc T TranDepartment of Radiation Oncology, University of Maryland, College Park, Baltimore, MD.ORCID 0000-0002-0147-0376
Edwin M PosadasUrologic Oncology Program & Uro-Oncology Research Laboratories, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA.ORCID 0000-0001-8649-1346
Chuan HeDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL.
Xiao-Long CuiDepartment of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, IL.
Jiaoti HuangDepartment of Pathology, Duke University, Durham, NC.
Wilbert ZwartNetherlands Cancer Institute, Oncode Institute, Amsterdam, the Netherlands.ORCID 0000-0002-9823-7289
Luke A GilbertHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
Christopher A MaherSiteman Cancer Center, Washington University, St. Louis, MO.ORCID 0000-0002-9035-603X
Paul C BoutrosDepartment of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0003-0553-7520
Kim N ChiVancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0002-3782-7226
Alan AshworthHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0003-1446-7878
Eric J SmallHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.
Housheng H He *Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.ORCID 0000-0003-2898-3363
Alexander W Wyatt *Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.ORCID 0000-0003-2399-0329
David A Quigley *Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-4726-1473
Felix Y Feng *Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA.ORCID 0000-0002-0963-7687
University of California, San Francisco · USUniversity of British Columbia · CAID Genomics (United States) · USUniversity of Toronto · CAUniversity of California, Los Angeles · USHoward Hughes Medical Institute · USOregon Health & Science University · USUniversity of California Davis Medical Center · USUniversity of Wisconsin–Madison · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZACedars-Sinai Medical Center · USDuke University · USHarvard University · USJames S. McDonnell Foundation · USMalmö University · SEMichigan Medicine · USOncode Institute · NLUniversity of Maryland, Baltimore · USUniversity of Pittsburgh · USUniversity of Southern California · US
Funding
Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Leigh Clarke · 1999 to 2026
$209.7MWomen's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Xinmin Li · 1985 to 2026
$134.5MStaff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Laura Marcu · 2002 to 2026
$84.9MTRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI John Kyung Lee · 2002 to 2026
$58.1MTissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Robert Timothy Dess · 2014 to 2026
$27.6MLabeling and sequencing of 5hmC and 5mC in DNA-RenewalR01HG006827 · NHGRI · UNIVERSITY OF CHICAGO · PI HE, CHUAN · 2012 to 2025
$7.2MMolecular Mechanisms of Castration Resistant Prostate Cancer Recurrence & Therapeutic StrategiesR01CA227025 · NCI · WASHINGTON UNIVERSITY · PI FENG, FELIX YI-CHUNG, MAHAJAN, NUPAM P · 2019 to 2023
$2.8MDNA repair alterations in metastatic prostate cancer: functional and therapeutic implicationsR01CA230516 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ASHWORTH, ALAN, FENG, FELIX YI-CHUNG · 2018 to 2022
$2.7MDevelopment of Protein Biomarkers in Post-DRE Urine for use in Liquid Biopsy of Prostate CancerU01CA214194 · NCI · EASTERN VIRGINIA MEDICAL SCHOOL · PI BOUTROS, PAUL CHRISTOPHER, KISLINGER, THOMAS · 2016 to 2021
$2.5MA GENETIC INTERACTION MAP OF THE HUMAN NUCLEUSDP2CA239597 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GILBERT, LUKE · 2018 to 2018
$2.4MDYNAMIC MOLECULAR EVOLUTION OF TREATMENT RESISTANT CANCERDP2CA271832 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI ZHAO, SHUANG · 2021 to 2024
$2.3MTargeting Prostate Cancer Lineage Plasticity with BET Bromodomain InhibitionR01CA251245 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ALUMKAL, JOSHI JAMES · 2020 to 2024
$1.9MNCI NIH HHS DP2 CA239597NCI NIH HHS DP2 CA271832NCI NIH HHS K08 CA226348NCI NIH HHS P30 CA016042NCI NIH HHS P30 CA082103NCI NIH HHS P30 CA093373NCI NIH HHS P50 CA097186NCI NIH HHS P50 CA186786NCI NIH HHS R01 CA208258NCI NIH HHS R01 CA227025NCI NIH HHS R01 CA230516NCI NIH HHS R01 CA251245NCI NIH HHS U01 CA214194NHGRI NIH HHS R01 HG006827NHGRI NIH HHS R01 HG012227
Abstract
Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first study integrating whole-genome 5hmC with DNA, 5mC, and transcriptome sequencing in clinical samples of benign, localized, and advanced prostate cancer. 5hmC is shown to mark activation of cancer drivers and downstream targets. Furthermore, 5hmC sequencing revealed profoundly altered cell states throughout the disease course, characterized by increased proliferation, oncogenic signaling, dedifferentiation, and lineage plasticity to neuroendocrine and gastrointestinal lineages. Finally, 5hmC sequencing of cell-free DNA from patients with metastatic disease proved useful as a prognostic biomarker able to identify an aggressive subtype of prostate cancer using the genes TOP2A and EZH2, previously only detectable by transcriptomic analysis of solid tumor biopsies. Overall, these findings reveal that 5hmC marks epigenomic activation in prostate cancer and identify hallmarks of prostate cancer progression with potential as biomarkers of aggressive disease. SIGNIFICANCE: In prostate cancer, 5-hydroxymethylcytosine delineates oncogene activation and stage-specific cell states and can be analyzed in liquid biopsies to detect cancer phenotypes. See related article by Wu and Attard, p. 3880.
Indexed as
5-MethylcytosineProstatic NeoplasmsBiopsyHumansMaleProstate5-hydroxymethylcytosine5-Methylcytosine
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