{
  "abstract": "Prostate cancer is characterized by profound clinical and molecular heterogeneity. Although its genomic heterogeneity is well characterized, its epigenomic heterogeneity remains less understood. We therefore created a compendium of 3,001 multiancestry prostate methylomes spanning normal tissue through localized disease of all grades to polymetastatic disease. A subset of 884 samples had multiomic DNA and/or RNA characterization. We identify four epigenomic subtypes that risk-stratify patients and reflect distinct evolutionary trajectories. We demonstrate extensive regulatory interplay between DNA copy number and methylation, with transcriptional consequences that vary across genes and disease stages. We define epigenetic dysregulation signatures for 15 important clinicomolecular features, creating predictive models for each. For example, we identify specific epigenetic features that predict patient outcome and are synergistic with clinical prognostic features. These results define a complex interplay between tumor genetics and epigenetics that converges to modify gene expression programs and clinical presentation, in part through modulation of epigenetic aging.\n\nSignificance:: We define the largest prostate cancer methylome resource to date, revealing four epigenomic subtypes that stratify cancers by their genetics, evolution, and clinical phenotypes. These data demonstrate that genome–epigenome interactions are stage-dependent, positioning DNA methylation as a central, clinically informative driver of prostate cancer heterogeneity.",
  "abstract_shown": true,
  "affiliations": [
    "Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California.",
    "Institute for Precision Health, University of California, Los Angeles, Los Angeles, California.",
    "Department of Human Genetics, University of California, Los Angeles, Los Angeles, California.",
    "Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.",
    "Division of Outcomes Research, Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, California.",
    "Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.",
    "Ontario Institute for Cancer Research, Toronto, Canada.",
    "Melbourne Bioinformatics, University of Melbourne, Parkville, Australia.",
    "Department of Medical Biophysics, University of Toronto, Toronto, Canada.",
    "Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.",
    "Department of Medical Biology, University of Melbourne, Parkville, Australia.",
    "Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.",
    "Australian BioCommons, University of Melbourne, Parkville, Australia.",
    "Department of Surgery, University of Melbourne, Parkville, Australia.",
    "Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California.",
    "Department of Radiation Oncology, University of Toronto, Toronto, Canada.",
    "Divisions of Radiation Oncology and Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore.",
    "Duke-NUS Medical School, Singapore, Singapore.",
    "Department of Urology, Western Health, Footscray, Australia.",
    "Department of Urology, Royal Melbourne Hospital, Parkville, Australia.",
    "Victorian Comprehensive Cancer Centre, Parkville, Australia.",
    "Division of Cancer Sciences-FBMH, CRUK Manchester Institute and Manchester Cancer Research Centre, University of Manchester, Manchester, United Kingdom."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 31,
  "authors": [
    {
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        0,
        1,
        2,
        3,
        4
      ],
      "name": "Jaron Arbet",
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        5
      ],
      "name": "Takafumi N. Yamaguchi",
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      "name": "Yu-Jia Shiah",
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      "name": "Rupert Hugh-White",
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      "name": "Adriana Wiggins",
      "orcid": "0009-0009-3396-9305"
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      "name": "Jieun Oh",
      "orcid": "0000-0002-8961-8645"
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      "name": "Nicole Zeltser",
      "orcid": "0000-0001-7246-2771"
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      ],
      "name": "Tsumugi Gebo",
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        6
      ],
      "name": "Adrien Foucal",
      "orcid": "0000-0003-1619-0753"
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      ],
      "name": "Robert Lesurf",
      "orcid": "0000-0001-7095-1491"
    },
    {
      "affs": [
        7
      ],
      "name": "Chol-Hee Jung",
      "orcid": "0000-0002-2992-3162"
    },
    {
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        0,
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      ],
      "name": "Rachel M.A. Dang",
      "orcid": "0000-0002-0347-3300"
    },
    {
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        2,
        3
      ],
      "name": "Raag Agrawal",
      "orcid": "0000-0001-8222-3117"
    },
    {
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        2
      ],
      "name": "Julie Livingstone",
      "orcid": "0000-0002-8424-3768"
    },
    {
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        3
      ],
      "name": "Adriana Salcedo",
      "orcid": "0000-0002-3365-2705"
    },
    {
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        6
      ],
      "name": "Cindy Q. Yao",
      "orcid": "0009-0009-4886-619X"
    },
    {
      "affs": [
        6
      ],
      "name": "Shadrielle Melijah G. Espiritu",
      "orcid": "0009-0002-0584-0626"
    },
    {
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        1,
        2,
        6,
        8
      ],
      "name": "Kathleen E. Houlahan",
      "orcid": "0000-0002-2273-2099"
    },
    {
      "affs": [
        6
      ],
      "name": "Fouad Yousif",
      "orcid": "0009-0005-2870-8515"
    },
    {
      "affs": [
        6
      ],
      "name": "Lawrence E. Heisler",
      "orcid": "0000-0002-1332-1802"
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    {
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        9,
        10
      ],
      "name": "Anthony T. Papenfuss",
      "orcid": "0000-0002-1102-8506"
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    {
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        11
      ],
      "name": "Michael Fraser",
      "orcid": "0000-0002-9303-9363"
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    {
      "affs": [
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        12,
        13
      ],
      "name": "Bernard J. Pope",
      "orcid": "0000-0002-4840-1095"
    },
    {
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        14
      ],
      "name": "Amar U. Kishan",
      "orcid": "0000-0002-4836-8483"
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    {
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        11,
        15
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      "name": "Alejandro Berlin",
      "orcid": "0000-0002-1880-6905"
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    {
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        15,
        16,
        17
      ],
      "name": "Melvin L.K. Chua",
      "orcid": "0000-0002-1648-1473"
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    {
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        13,
        18,
        19
      ],
      "name": "Niall M. Corcoran",
      "orcid": "0000-0003-4483-6945"
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    {
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        11
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      "name": "Theodorus van der Kwast",
      "orcid": "0000-0001-8640-5786"
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        20
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      "name": "Christopher M. Hovens",
      "orcid": "0000-0002-0610-1289"
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    {
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        11,
        15,
        21
      ],
      "name": "Robert G. Bristow",
      "orcid": "0000-0002-8553-9544"
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    {
      "affs": [
        5
      ],
      "name": "Paul C. Boutros",
      "orcid": "0000-0003-0553-7520"
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  "bibtex": "https://research.draconitic.com/paper/f2hxg5xm2pc8q.bib",
  "cited_by": 2,
  "doi": "10.1158/2159-8290.cd-25-0761",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13725346/",
  "id": "f2hxg5xm2pc8q",
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  "landing_url": "https://doi.org/10.1158/2159-8290.cd-25-0761",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Artificial Intelligence & Machine Learning"
    ],
    [
      "heading",
      "Computational Methods"
    ],
    [
      "heading",
      "DNA methylation"
    ],
    [
      "heading",
      "Epigenetics"
    ],
    [
      "heading",
      "Genitourinary Cancers"
    ],
    [
      "heading",
      "Prostate Cancer"
    ],
    [
      "heading",
      "Research Articles"
    ],
    [
      "heading",
      "Software"
    ],
    [
      "heading",
      "Systems Biology"
    ],
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W4407384944",
  "pdf_url": null,
  "pmcid": "PMC13725346",
  "pmid": "42307031",
  "published": "2026-06-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/f2hxg5xm2pc8q.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:23:45Z",
      "native_id": "PMC13725346",
      "source": "pmc",
      "url": "https://doi.org/10.1158/2159-8290.cd-25-0761"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Systems Biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "The Landscape of Prostate Tumor Methylation",
  "title_text": "The Landscape of Prostate Tumor Methylation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:21:38Z",
  "url": "https://research.draconitic.com/paper/f2hxg5xm2pc8q",
  "venue": "Cancer Discovery",
  "versions": []
}