{
  "abstract": "Werner syndrome, a premature-aging disorder caused by inherited loss of the WRN helicase, predisposes to a narrow set of cancers, including melanoma and sarcoma, through mechanisms that have been unclear. WRN resolves the secondary structures that TA-dinucleotide repeats form, a role established for the expanded repeats of mismatch-repair-deficient cancers. We show that WRN loss also destabilizes native, unexpanded TA-rich tandem repeats, which become fragile sites where chromosomes break and rearrange. In melanoma these rearrangements recurrently produce an identical 15.7Mb-long deletion that transcriptionally activates TERT, the earliest driver of these tumors, and separately disrupt tumor suppressors such as CDKN2A/B and NF1. The same class of rearrangement occurs in WRN-deficient cancers of other types. WRN deficiency is thus a source of instability at TA-rich tandem repeats that generates oncogenic rearrangements.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "name": "Meng Wang",
      "orcid": "0000-0003-3209-1026"
    },
    {
      "name": "Hui Pan"
    },
    {
      "name": "Anastasia Samarkina"
    },
    {
      "name": "Austin John Escobar"
    },
    {
      "name": "Noel Cruz Pacheco"
    },
    {
      "name": "Satoru Mizuhashi"
    },
    {
      "name": "Jamie D. Aquino"
    },
    {
      "name": "Katy K. Tsai"
    },
    {
      "name": "Adil I. Daud"
    },
    {
      "name": "Ivan EI-Sayed"
    },
    {
      "name": "Haruto Nishida"
    },
    {
      "name": "Sakuhei Fujiwara"
    },
    {
      "name": "Takashi Hirano"
    },
    {
      "name": "Sine Phelan"
    },
    {
      "name": "Allan O’Keefe"
    },
    {
      "name": "Sean Dinneen"
    },
    {
      "name": "A. Hunter Shain"
    },
    {
      "name": "Makoto Goto"
    },
    {
      "name": "Iwei Yeh"
    },
    {
      "name": "Boris C. Bastian"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2498atazh3ehq.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.16.758976",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.758976v1.full",
  "id": "2498atazh3ehq",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.758976v1",
  "language": "en",
  "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",
      "cancer biology"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|DNA Repair Mechanisms"
    ]
  ],
  "openalex": "W7223224737",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.758976v1.full.pdf",
  "pmcid": "PMC13738482",
  "pmid": "42995830",
  "published": "2026-10-16",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/2498atazh3ehq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:12Z",
      "native_id": "10.64898/2026.10.16.758976",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.16.758976v1"
    },
    {
      "first_seen": "2026-11-09T12:23:27Z",
      "native_id": "PMC13738482",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.16.758976"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "WRN deficiency generates oncogenic rearrangements at TA-rich tandem repeats",
  "title_text": "WRN deficiency generates oncogenic rearrangements at TA-rich tandem repeats",
  "type": "preprint",
  "updated_at": "2026-11-09T12:23:27Z",
  "url": "https://research.draconitic.com/paper/2498atazh3ehq",
  "venue": "bioRxiv",
  "versions": []
}