{
  "abstract": "The contribution of telomere length, telomerase activation, and alternative lengthening of telomeres (ALT) to individual sarcoma subtypes remains unclear. We analyzed 11,792 patients with sarcoma sequenced across 19 centers in AACR Project GENIE v20.0, defining telomerase activation as TERT promoter mutation, amplification, or rearrangement and using ATRX/DAXX inactivation as the ALT proxy, with denominators restricted to patients whose assay interrogated the relevant locus. Findings were tested for TERT expression in The Cancer Genome Atlas, for overall survival in MSK-IMPACT 50K, and for replication in an independent Foundation Medicine cohort; Mendelian randomization in FinnGen tested germline telomere length. Telomerase activation (8.8%) and ATRX/DAXX loss (8.0%) segregated by histology and co-occurred less often than expected across subtypes (Mantel-Haenszel odds ratio [OR], 0.52; 95% CI, 0.29 to 0.92). In MDM2-amplified dedifferentiated liposarcoma (DDLPS), telomerase was activated through TERT amplification (17.2%) or rearrangement (2.7%) and never through promoter mutation (0/261), and never co-occurred with ATRX/DAXX loss (0/49; P = .011). TERT-amplified tumors expressed TERT (P = .002), and amplification was largely focal. Telomere maintenance alterations were present in 28.0% of DDLPS versus 8.7% of well-differentiated liposarcoma (P < .001) and predicted shorter overall survival in DDLPS (hazard ratio, 2.04; 95% CI, 1.23 to 3.39; P = .005). ATRX/DAXX loss was more frequent in uterine than extrauterine leiomyosarcoma in GENIE (adjusted OR, 1.96) and in the independent cohort (OR, 1.95; both P < .001). Genetically longer telomeres were associated with liposarcoma (OR per SD, 4.10; 95% CI, 2.15 to 7.81). Telomere maintenance in sarcoma is therefore histology-specific; in liposarcoma it is acquired at dedifferentiation through focal TERT amplification or ALT rather than promoter mutation, and it identifies DDLPS with inferior survival.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University School of Medicine"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "M. Pan"
    },
    {
      "name": "J. Chi"
    },
    {
      "name": "M. Y. Zhou"
    },
    {
      "name": "N. Bui"
    },
    {
      "name": "K. Ganjoo"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/36428ep86mwrc.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.28.26364135",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.09.28.26364135v1.full",
  "id": "36428ep86mwrc",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.09.28.26364135v1",
  "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": [
    [
      "medrxiv",
      "oncology"
    ],
    [
      "openalex",
      "2737|Telomeres, Telomerase, and Senescence"
    ]
  ],
  "openalex": "W7214702717",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.09.28.26364135v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/36428ep86mwrc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:39Z",
      "native_id": "10.64898/2026.09.28.26364135",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.09.28.26364135v3"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "medrxiv:oncology",
      "subfield": "oncology"
    }
  ],
  "title": "Somatic and Germline Telomere Biology in Sarcoma: Telomere Maintenance Is Acquired at Liposarcoma Dedifferentiation, and Genetically Longer Telomeres Are Associated With Liposarcoma Risk",
  "title_text": "Somatic and Germline Telomere Biology in Sarcoma: Telomere Maintenance Is Acquired at Liposarcoma Dedifferentiation, and Genetically Longer Telomeres Are Associated With Liposarcoma Risk",
  "type": "preprint",
  "updated_at": "2026-10-30T12:21:43Z",
  "url": "https://research.draconitic.com/paper/36428ep86mwrc",
  "venue": "medRxiv",
  "versions": []
}