{
  "abstract": "Undifferentiated embryonal sarcoma of the liver (UESL) and mesenchymal hamartoma of the liver (MHL) are rare pediatric liver tumors with poorly understood oncogenic mechanisms. Although UESL occasionally arises from MHL, the relationship between these entities remains elusive. Here, we conducted comprehensive multi-omics profiling of 18 UESL and six MHL cases, and identified structural variants (SVs) involving the C19MC miRNA cluster in all tumors, resulting in robust overexpression of C19MC miRNAs. While mutations in TP53 were detected in all UESL samples, they were absent from MHL. Functional studies demonstrated that overexpression of C19MC miRNAs alone was insufficient for transformation, but acted synergistically with TP53 loss to drive oncogenicity. Spatial transcriptomics performed on a tumor sample containing a composite MHL-UESL lesion revealed pseudo-temporal gene expression trajectories and clonal diversification. Collectively, these findings delineate a stepwise malignant transformation from MHL to UESL, and reveal the underlying cooperative genetic events.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto, Japan",
    "Department of Hematology and Oncology, Shizuoka Children’s Hospital, Shizuoka, Japan",
    "Department of Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan",
    "Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo, Japan",
    "Department of Pediatric Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan",
    "Department of Pathology, Kanagawa Children’s Medical Center, Yokohama, Japan",
    "Department of Pathology, National Center for Child Health and Development, Tokyo, Japan",
    "Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan",
    "The Hakubi Center for Advanced Research, Kyoto University, Kyoto, Japan",
    "Division of Genome Analysis Platform Development, National Cancer Center Institute, Tokyo, Japan",
    "Department of Childhood Cancer Data Management, Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan",
    "Department of Pediatric Surgery, Chiba University Graduate School of Medicine, Chiba, Japan",
    "Department of Pediatrics, Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-Kofukai, Osaka, Japan",
    "Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan",
    "Department of Pediatric Hematology/Oncology, Osaka City General Hospital, Osaka, Japan",
    "Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan",
    "Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan",
    "Laboratory Animal Research Department, Central Institute for Experimental Medicine and Life Science, Kawasaki, Japan",
    "Department of Biomedical Science, Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan",
    "Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto, Japan",
    "Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden",
    "Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, Fukui, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 35,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yoshinori Uchihara"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Keiji Tasaka"
    },
    {
      "affs": [
        0
      ],
      "name": "Takashi Mikami"
    },
    {
      "affs": [
        2
      ],
      "name": "Yosuke Yamada"
    },
    {
      "affs": [
        2
      ],
      "name": "Hiroaki Ito"
    },
    {
      "affs": [
        3
      ],
      "name": "Hajime Okita"
    },
    {
      "affs": [
        0
      ],
      "name": "Ryunosuke Tojo"
    },
    {
      "affs": [
        0
      ],
      "name": "Ryo Akazawa"
    },
    {
      "affs": [
        0
      ],
      "name": "Kiyotaka Isobe"
    },
    {
      "affs": [
        0
      ],
      "name": "Tatsuya Kamitori"
    },
    {
      "affs": [
        0
      ],
      "name": "Masahiko Nishitani-Isa"
    },
    {
      "affs": [
        0
      ],
      "name": "Hirohito Kubota"
    },
    {
      "affs": [
        0
      ],
      "name": "Satoshi Saida"
    },
    {
      "affs": [
        0
      ],
      "name": "Itaru Kato"
    },
    {
      "affs": [
        4
      ],
      "name": "Tatsuya Okamoto"
    },
    {
      "affs": [
        4
      ],
      "name": "Eri Ogawa"
    },
    {
      "affs": [
        4
      ],
      "name": "Hideaki Okajima"
    },
    {
      "affs": [
        5
      ],
      "name": "Yukichi Tanaka"
    },
    {
      "affs": [
        6
      ],
      "name": "Takako Yoshioka"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Nobuyuki Kakiuchi"
    },
    {
      "affs": [
        9
      ],
      "name": "Yuichi Shiraishi"
    },
    {
      "affs": [
        10
      ],
      "name": "Tetsuya Takimoto"
    },
    {
      "affs": [
        11
      ],
      "name": "Shugo Komatsu"
    },
    {
      "affs": [
        12
      ],
      "name": "Mitsutaka Shiota"
    },
    {
      "affs": [
        13
      ],
      "name": "Kazuko Kudo"
    },
    {
      "affs": [
        14
      ],
      "name": "Hiroyuki Fujisaki"
    },
    {
      "affs": [
        15
      ],
      "name": "Masahiro Sekiguchi"
    },
    {
      "affs": [
        16
      ],
      "name": "Yoshiyuki Takahashi"
    },
    {
      "affs": [
        17
      ],
      "name": "Mamoru Ito"
    },
    {
      "affs": [
        17
      ],
      "name": "Tatsutoshi Nakahata"
    },
    {
      "affs": [
        2
      ],
      "name": "Hironori Haga"
    },
    {
      "affs": [
        18
      ],
      "name": "Eiso Hiyama"
    },
    {
      "affs": [
        7,
        19,
        20
      ],
      "name": "Seishi Ogawa"
    },
    {
      "affs": [
        0,
        21
      ],
      "name": "Katsutsugu Umeda"
    },
    {
      "affs": [
        0
      ],
      "name": "Junko Takita"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/45fmem6g33qna.bib",
  "cited_by": 0,
  "doi": "10.1038/s41698-026-01563-2",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13740288/",
  "id": "45fmem6g33qna",
  "issns": [
    "2397-768X"
  ],
  "landing_url": "https://doi.org/10.1038/s41698-026-01563-2",
  "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",
      "Article"
    ],
    [
      "openalex",
      "2730|Sarcoma Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7168288647",
  "pdf_url": null,
  "pmcid": "PMC13740288",
  "pmid": "42448860",
  "published": "2026-07-14",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/45fmem6g33qna.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T12:21:34Z",
      "native_id": "PMC13740288",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41698-026-01563-2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Sarcoma Diagnosis and Treatment",
      "subfield": "oncology"
    }
  ],
  "title": "Stepwise malignant transformation from MHL to UESL via activation of C19MC and loss of TP53",
  "title_text": "Stepwise malignant transformation from MHL to UESL via activation of C19MC and loss of TP53",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:21:34Z",
  "url": "https://research.draconitic.com/paper/45fmem6g33qna",
  "venue": "NPJ Precision Oncology",
  "versions": []
}