{
  "abstract": "Background: Endometrial cancer with somatic POLE exonuclease domain mutations (EDMs) has a highly favorable prognosis; however, the clinical implications of non-hotspot EDMs in POLE remain unclear.\n\nMaterials and methods: In 793 patients with endometrial cancer enrolled at the National Cancer Center and Juntendo University Hospitals, 25 prespecified variants were screened using the Luminex assay. Whole-exome sequencing (WES) was carried out to evaluate 54 patients with hotspot and non-hotspot EDMs. In patients with endometrial cancer (n = 4864) registered in Genomics Evidence Neoplasia Information Exchange (GENIE), those harboring hotspot EDMs were matched with randomly sampled patients without EDMs, and a polymerase epsilon (POLE) score for gene panel testing was developed.\n\nResults: In our cohort, POLE-EDMs, including hotspot (n = 91) and non-hotspot (n = 12) EDMs, were identified in 103 (12.9%) of 793 patients. The prevalence of grade 3 and advanced-stage endometrial cancer was higher in patients with non-hotspot EDMs than in those with hotspot EDMs. WES analysis of 54 patients revealed no significant differences in genomic mutations between the groups, and four non-hotspot EDMs were identified. A POLE-specific mutational signature was observed in tumors with EDM. In addition, the POLE score criteria were developed based on hotspot EDMs using the GENIE cohort, achieving a detection sensitivity of 0.94. Using the established POLE score, we identified nine non-hotspot EDMs.\n\nConclusions: We identified 13 novel candidate non-hotspot EDMs using a newly established POLE score for gene panels and demonstrated an association between non-hotspot EDMs and favorable prognosis. The identification of additional non-hotspot EDMs will facilitate precise molecular classification of endometrial cancer.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Genome Biology, National Cancer Center Research Institute, Tokyo, Japan",
    "Department of Obstetrics and Gynecology, Juntendo University Faculty of Medicine, Tokyo, Japan",
    "Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan",
    "Department of Gynecology, National Cancer Center Hospital, Tokyo, Japan",
    "Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan",
    "Medical & Biological Laboratories Co, Ltd (MBL), Tokyo, Japan",
    "Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan",
    "Department of Obstetrics and Gynecology, Showa Medical University School of Medicine, Tokyo, Japan",
    "Department of Obstetrics and Gynecology, Nippon Medical School, Tokyo, Japan",
    "Department of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan",
    "Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan",
    "Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan",
    "Division of Medical AI Research and Development, National Cancer Center Research Institute, Tokyo, Japan",
    "AI Medical Engineering Team, RIKEN Center for Advanced Intelligence Project, Tokyo, Japan",
    "Division of Biostatistical Research, National Cancer Center Institute of Cancer Control, Tokyo, Japan",
    "Teikyo University Graduate School of Public Health, Tokyo, Japan",
    "Biostatistics Division, Center for Research Administration and Support, National Cancer Center, Tokyo, Japan",
    "Division of Bioinformatics, National Cancer Center Research Institute, Tokyo, Japan",
    "Department of Diagnostics and Therapeutics of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 27,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "T. Kawai"
    },
    {
      "affs": [
        2
      ],
      "name": "H. Yoshida"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "M. Kobayashi Kato"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "M. Yamaguchi"
    },
    {
      "affs": [
        0,
        3,
        4
      ],
      "name": "T. Shiraishi"
    },
    {
      "affs": [
        5
      ],
      "name": "H. Okada"
    },
    {
      "affs": [
        5
      ],
      "name": "T. Kondo"
    },
    {
      "affs": [
        6
      ],
      "name": "T. Koyama"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "D. Higuchi"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "T. Harazawa"
    },
    {
      "affs": [
        0,
        8,
        9
      ],
      "name": "A. Ikki"
    },
    {
      "affs": [
        10
      ],
      "name": "T. Yamanaka"
    },
    {
      "affs": [
        11
      ],
      "name": "A. Tateishi"
    },
    {
      "affs": [
        12,
        13
      ],
      "name": "M. Komatsu"
    },
    {
      "affs": [
        12,
        13
      ],
      "name": "R. Hamamoto"
    },
    {
      "affs": [
        14,
        15
      ],
      "name": "A. Kuchiba"
    },
    {
      "affs": [
        14,
        16
      ],
      "name": "T. Shibata"
    },
    {
      "affs": [
        17
      ],
      "name": "J. Nishino"
    },
    {
      "affs": [
        4
      ],
      "name": "W. Yamagami"
    },
    {
      "affs": [
        7
      ],
      "name": "K. Matsumoto"
    },
    {
      "affs": [
        3
      ],
      "name": "T. Kato"
    },
    {
      "affs": [
        0
      ],
      "name": "T. Kohno"
    },
    {
      "affs": [
        1,
        18
      ],
      "name": "E. Yoshida"
    },
    {
      "affs": [
        1
      ],
      "name": "Y. Terao"
    },
    {
      "affs": [
        10
      ],
      "name": "K. Yonemori"
    },
    {
      "affs": [
        3
      ],
      "name": "M. Ishikawa"
    },
    {
      "affs": [
        0,
        9
      ],
      "name": "K. Shiraishi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/493yfr6a3nejc.bib",
  "cited_by": 0,
  "doi": "10.1016/j.esmoop.2026.108605",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13733457/",
  "id": "493yfr6a3nejc",
  "issns": [
    "2059-7029"
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  "landing_url": "https://doi.org/10.1016/j.esmoop.2026.108605",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
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      "openalex",
      "2729|Endometrial and Cervical Cancer Treatments"
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  "openalex": "W7224349582",
  "pdf_url": "https://www.esmoopen.com/article/S2059-7029(26)02550-0/pdf",
  "pmcid": "PMC13733457",
  "pmid": "42956692",
  "published": "2026-10-29",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/493yfr6a3nejc.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:23:14Z",
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      "url": "https://doi.org/10.1016/j.esmoop.2026.108605"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2729|Endometrial and Cervical Cancer Treatments",
      "subfield": "reproductive-child"
    }
  ],
  "title": "Identification and prognostic value of non-hotspot POLE exonuclease domain mutations in endometrial cancer",
  "title_text": "Identification and prognostic value of non-hotspot POLE exonuclease domain mutations in endometrial cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:23:14Z",
  "url": "https://research.draconitic.com/paper/493yfr6a3nejc",
  "venue": "ESMO Open",
  "versions": []
}