{
  "abstract": "Background: POLE -mutated endometrial carcinomas are associated with an excellent prognosis and have become an integral component of the molecular classification of endometrial carcinoma. However, the pathogenicity of many rare non-hotspot POLE exonuclease-domain variants remains uncertain, particularly when they occur in tumors harboring additional molecular alterations that may confound molecular classification.\n\nMethods: Histopathologic findings and immunohistochemical expression of mismatch repair proteins and p53 were evaluated. Targeted next-generation sequencing of tumor tissue was performed to characterize genomic alterations, microsatellite instability, tumor mutational burden, and the mutational spectrum. The non-hotspot POLE p.T278K variant was evaluated using the León-Castillo scoring framework. MLH1 promoter methylation was assessed by methylation-specific PCR to further characterize the subclonal MLH1/PMS2 loss.\n\nCase summary: A 59-year-old woman with endometrioid endometrial carcinoma underwent total hysterectomy with surgical staging. Targeted next-generation sequencing identified a rare non-hotspot POLE exonuclease-domain variant, c.833C>A (p.T278K), together with two MSH6 frameshift variants, c.3261del (p.F1088Sfs*2) and c.3261dup (p.F1088Lfs*5). The tumor demonstrated an ultramutated genomic profile with a tumor mutational burden of 370.0 mutations/Mb and an MSI-H phenotype. Immunohistochemistry demonstrated subclonal loss of MLH1, PMS2, and MSH6 with retained MSH2 expression; MLH1 promoter methylation was also detected.\n\nConclusion: This case adds clinicopathological and molecular evidence supporting the biological significance of the rare POLE p.T278K variant and illustrates a practical approach for interpreting uncommon POLE exonuclease-domain variants in endometrial carcinomas with multiple molecular classifiers. Accurate identification of the dominant molecular classifier is critical for appropriate molecular classification, prognostic assessment, and clinical management.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan"
  ],
  "article_type": "case report",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yuxuan Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Huimei Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Huixing Yan"
    },
    {
      "affs": [
        0
      ],
      "name": "Haoping Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinyue Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiuli Teng"
    },
    {
      "affs": [
        0
      ],
      "name": "Longxin Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jinwen Ye"
    },
    {
      "affs": [
        0
      ],
      "name": "Zeng Yuan"
    },
    {
      "affs": [
        0
      ],
      "name": "Qing Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2gk0gxsfpvxa4.bib",
  "cited_by": 0,
  "doi": "10.3389/fonc.2026.1964637",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13716634/?tool=EBI",
  "id": "2gk0gxsfpvxa4",
  "issns": [
    "2234-943X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1964637/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Case Report"
    ],
    [
      "openalex",
      "2734|Genetic factors in colorectal cancer"
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  ],
  "openalex": "W7222181695",
  "pdf_url": "https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1964637/pdf",
  "pmcid": "PMC13716634",
  "pmid": "42959168",
  "published": "2026-10-15",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/2gk0gxsfpvxa4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:13Z",
      "native_id": "10.3389/fonc.2026.1964637",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fonc.2026.1964637/full"
    },
    {
      "first_seen": "2026-10-31T00:20:37Z",
      "native_id": "PMC:PMC13716634",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13716634"
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    {
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      "native_id": "MED:42959168",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42959168"
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    {
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      "url": "https://doi.org/10.3389/fonc.2026.1964637"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:2234-943X",
      "subfield": "oncology"
    }
  ],
  "title": "Case Report: Endometrial carcinoma harboring a rare POLE p.T278K variant and dual MSH6 frameshift variants",
  "title_text": "Case Report: Endometrial carcinoma harboring a rare POLE p.T278K variant and dual MSH6 frameshift variants",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:07Z",
  "url": "https://research.draconitic.com/paper/2gk0gxsfpvxa4",
  "venue": "Frontiers in Oncology",
  "versions": []
}