{
  "abstract": "Cancer genomes harbor extensive somatic genetic and epigenetic variation, yet large portions of the genome remain inaccessible to conventional reference-based analyses. Here, we demonstrate that pairing a near-telomere-to-telomere (near-T2T) diploid assembly of a donor with deep short- and long-read sequencing of their melanoma reveals that 16% of somatic variants localize to sequences absent from GRCh38, with satellite repeats acting as hotspots for UV-associated mutagenesis. Centromere kinetochore binding domains emerge as focal sites of chromosome arm aneuploidy breakpoints and somatic genetic variation, features we further demonstrate are also present in non-cancerous tissues. By contrast, extensive epigenetic remodeling of kinetochore binding domains appears specific to oncogenesis. Single-molecule telomere analyses reconstruct the cycle of telomere erosion and telomerase-mediated extension during tumor evolution, while haplotype-resolved chromatin maps reveal widespread somatic epimutations impacting regulatory elements. Together, these findings define previously inaccessible dimensions of somatic variation and establish a framework for telomere-to-telomere studies of human mosaicism.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA",
    "Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA",
    "Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA",
    "Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA",
    "Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, WA 98101, USA",
    "Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; Northwest Genomics Center, University of Washington, Seattle, WA, USA",
    "Coriell Institute for Medical Research, Camden, NJ 08103, USA",
    "Pacific Northwest Research Institute, Seattle, WA, USA",
    "Broad Institute of MIT and Harvard, Cambridge, MA, USA",
    "Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; Computational Biology Division, Fred Hutchinson Cancer Center, Seattle, WA, USA",
    "Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA",
    "Department of Genetics, School of Medicine, Stanford University, Stanford, CA, USA; Biohub, San Francisco, San Francisco, CA, USA",
    "Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA; Brotman Baty Institute for Precision Medicine, Seattle, WA, USA. Electronic address: absterga@uw.edu"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 44,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Min-Hwan Sohn",
      "orcid": "0000-0001-7563-6781"
    },
    {
      "affs": [
        1
      ],
      "name": "Danilo Dubocanin",
      "orcid": "0000-0003-0330-5814"
    },
    {
      "affs": [
        2
      ],
      "name": "Mitchell Robert Vollger",
      "orcid": "0000-0002-8651-1615"
    },
    {
      "affs": [
        3
      ],
      "name": "Youngjun Kwon",
      "orcid": "0000-0002-5024-2134"
    },
    {
      "affs": [
        0
      ],
      "name": "Anna Minkina",
      "orcid": "0000-0002-7989-4478"
    },
    {
      "affs": [
        3
      ],
      "name": "Katherine M. Munson",
      "orcid": "0000-0001-8413-6498"
    },
    {
      "affs": [
        3
      ],
      "name": "Samuel F. M. Hart",
      "orcid": "0000-0002-5068-2199"
    },
    {
      "affs": [
        0
      ],
      "name": "Jane Ranchalis"
    },
    {
      "affs": [
        4
      ],
      "name": "Nancy L. Parmalee",
      "orcid": "0009-0003-4262-820X"
    },
    {
      "affs": [
        0
      ],
      "name": "Adriana Estela Sedeño-Cortés",
      "orcid": "0000-0001-7959-8970"
    },
    {
      "affs": [
        4
      ],
      "name": "Jeffrey Ou",
      "orcid": "0000-0002-7067-0056"
    },
    {
      "affs": [
        0
      ],
      "name": "Shane J. Neph",
      "orcid": "0000-0003-2962-8777"
    },
    {
      "affs": [
        4
      ],
      "name": "Natalie Y.T. Au",
      "orcid": "0009-0006-4339-702X"
    },
    {
      "affs": [
        0
      ],
      "name": "Stephanie C. Bohaczuk",
      "orcid": "0000-0001-8802-6579"
    },
    {
      "affs": [
        5
      ],
      "name": "Brianne Carroll"
    },
    {
      "affs": [
        5
      ],
      "name": "Christian D. Frazar",
      "orcid": "0000-0002-6730-4426"
    },
    {
      "affs": [
        3
      ],
      "name": "William T. Harvey",
      "orcid": "0000-0003-0646-7528"
    },
    {
      "affs": [
        3
      ],
      "name": "Kendra Hoekzema",
      "orcid": "0000-0002-8058-0177"
    },
    {
      "affs": [
        5
      ],
      "name": "Huang Meng-fan"
    },
    {
      "affs": [
        5
      ],
      "name": "Caitlin N. Jacques",
      "orcid": "0000-0002-7259-4237"
    },
    {
      "affs": [
        4
      ],
      "name": "Dana M. Jensen",
      "orcid": "0000-0001-5981-5886"
    },
    {
      "affs": [
        5
      ],
      "name": "J. Thomas Kolar"
    },
    {
      "affs": [
        1
      ],
      "name": "Rosa Lee"
    },
    {
      "affs": [
        3
      ],
      "name": "Jiadong Lin",
      "orcid": "0000-0002-8116-5901"
    },
    {
      "affs": [
        4
      ],
      "name": "Kelsey A. Loy",
      "orcid": "0000-0003-3792-5130"
    },
    {
      "affs": [
        3
      ],
      "name": "Taralynn Mack",
      "orcid": "0000-0003-1043-2950"
    },
    {
      "affs": [
        3
      ],
      "name": "Yizi Mao",
      "orcid": "0000-0001-5743-6831"
    },
    {
      "affs": [
        6
      ],
      "name": "Matthew W. Mitchell",
      "orcid": "0000-0002-6947-0495"
    },
    {
      "affs": [
        4
      ],
      "name": "Meranda M Pham"
    },
    {
      "affs": [
        6
      ],
      "name": "Laura Scheinfeldt",
      "orcid": "0000-0001-6529-6701"
    },
    {
      "affs": [
        6
      ],
      "name": "Gretchen Smith"
    },
    {
      "affs": [
        5
      ],
      "name": "Erica Ryke",
      "orcid": "0000-0002-4056-1465"
    },
    {
      "affs": [
        5
      ],
      "name": "Joshua D. Smith"
    },
    {
      "affs": [
        4
      ],
      "name": "Lila Sutherlin"
    },
    {
      "affs": [
        2
      ],
      "name": "Elliott G. Swanson",
      "orcid": "0000-0002-0351-6446"
    },
    {
      "affs": [
        5
      ],
      "name": "Jeffrey M. Weiss"
    },
    {
      "affs": [
        7
      ],
      "name": "Claudia M.B. Carvalho"
    },
    {
      "affs": [
        8
      ],
      "name": "Tim H. H. Coorens",
      "orcid": "0000-0002-5826-3554"
    },
    {
      "affs": [
        9
      ],
      "name": "Kelley Harris"
    },
    {
      "affs": [
        5
      ],
      "name": "Chia‐Lin Wei"
    },
    {
      "affs": [
        10
      ],
      "name": "Evan E. Eichler",
      "orcid": "0000-0002-8246-4014"
    },
    {
      "affs": [
        11
      ],
      "name": "Nicolas Altemose",
      "orcid": "0000-0002-7231-6026"
    },
    {
      "affs": [
        4
      ],
      "name": "James T. Bennett"
    },
    {
      "affs": [
        12
      ],
      "name": "Andrew B. Stergachis",
      "orcid": "0000-0002-1299-3674"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c7s3cgxk9cwcg.bib",
  "cited_by": 15,
  "doi": "10.1016/j.cell.2026.09.033",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13722029/",
  "id": "c7s3cgxk9cwcg",
  "issns": [
    "0092-8674",
    "1097-4172"
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  "landing_url": "https://doi.org/10.1016/j.cell.2026.09.033",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "1306|Cancer Genomics and Diagnostics"
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  "openalex": "W7222160977",
  "pdf_url": null,
  "pmcid": "PMC13722029",
  "pmid": "42880233",
  "published": "2026-10-01",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/c7s3cgxk9cwcg.ris",
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      "url": "https://doi.org/10.1016/j.cell.2026.09.033"
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  "subjects": [
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      "field": "medicine",
      "origin": "openalex:1306|Cancer Genomics and Diagnostics",
      "subfield": "oncology"
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  ],
  "title": "A telomere-to-telomere map of somatic mutation burden and functional impact in a cancer",
  "title_text": "A telomere-to-telomere map of somatic mutation burden and functional impact in a cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:05Z",
  "url": "https://research.draconitic.com/paper/c7s3cgxk9cwcg",
  "venue": "Cell",
  "versions": []
}