{
  "abstract": "DNA methylation aberrations and variability are pervasive features of cancer, yet their relationship with chromatin regulation remains incompletely understood. Across hundreds of matched tumor-normal methylomes, regions with the highest methylation entropy in both tumor and normal tissues were consistently enriched for PRC2-associated factors. In tumors, inter-sample methylation variability was increased across the full range of PRC2-associated levels, while mean methylation progressively increased from low- to high-PRC2-binding regions; this gradient was substantially weaker in matched normal tissues. PRC2-associated regions with higher DNA methylation levels were preferentially associated with poised and repressed chromatin states, reduced chromatin accessibility, and reduced gene expression. Independent normal-precancer-cancer cohorts showed that this PRC2-associated methylation state emerges early, with precancerous and malignant tissues displaying highly similar profiles that are distinct from those of healthy tissues. Single-cell colon cancer methylomes independently confirmed increased methylation entropy at PRC2 regions. Higher PRC2-region entropy was associated with scores reflecting hypoxic states, aggressive tumor features, and poorer survival outcomes. Collectively, these findings identify PRC2-binding regions as hotspots of DNA methylation variability that become dysregulated during tumorigenesis.",
  "abstract_shown": true,
  "affiliations": [
    "Fingerprint Diagnostics"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "name": "D. Bukovec"
    },
    {
      "name": "M. S. Misheva"
    },
    {
      "name": "M. Gjorgjievska"
    },
    {
      "affs": [
        0
      ],
      "name": "G. Kungulovski"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e126t8wx2f8hm.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.11.758285",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758285v1.full",
  "id": "e126t8wx2f8hm",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758285v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ],
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W7221660654",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758285v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-11",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e126t8wx2f8hm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:32Z",
      "native_id": "10.64898/2026.10.11.758285",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.11.758285v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "PRC2-binding regions are hotspots of DNA methylation entropy in pre-cancer and cancer",
  "title_text": "PRC2-binding regions are hotspots of DNA methylation entropy in pre-cancer and cancer",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:32Z",
  "url": "https://research.draconitic.com/paper/e126t8wx2f8hm",
  "venue": "bioRxiv",
  "versions": []
}