{
  "abstract": "Perivascular epithelioid cell neoplasms (PEComas) are ultra-rare mesenchymal tumors lacking a molecular classification to guide therapy. Here we perform comprehensive multi-omic profiling of an unselected PEComa cohort. We identify frequent MITF rearrangements involving actin gene partners (ACTA2, ACTG1 and ACTB). Anatomical stratification reveals cyclin-dependent kinase module mutations in gynecologic tumors, whereas soft tissue, gastrointestinal, and pelvic tumors lacked mTOR pathway alterations but are enriched for TFE3/MITF rearrangements. Transcriptomic analysis defines four subtypes with distinct lineage programs-melanocytic, mesenchymal, or adipogenic-as well as unique mutational patterns and clinical behaviors. Notably, an aggressive stem-like subtype enriched for TP53/RB1 mutations exhibits high proliferation, activation of embryonic and Hedgehog signaling, immune infiltration, and resistance to mTOR inhibitors, but potential responsiveness to immunotherapy. Single-nucleus RNA sequencing reveals intra-tumoral heterogeneity within this subtype, including divergent inflammatory states. Together, these findings establish a molecular classification framework and identify actionable vulnerabilities in PEComa.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 35,
  "authors": [
    {
      "name": "Justine Gantzer"
    },
    {
      "name": "Xiaofan Lu"
    },
    {
      "name": "Céline Charon-Barra"
    },
    {
      "name": "Charles Vinson"
    },
    {
      "name": "Noëlle Weingertner"
    },
    {
      "name": "Antonin Fattori"
    },
    {
      "name": "Marie-Pierre Chenard"
    },
    {
      "name": "Damien Plassard"
    },
    {
      "name": "Serge Vicaire"
    },
    {
      "name": "François Le Loarer"
    },
    {
      "name": "Maud Toulmonde"
    },
    {
      "name": "Marie Karanian"
    },
    {
      "name": "Mehdi Brahmi"
    },
    {
      "name": "Carine Ngo"
    },
    {
      "name": "Axel Le Cesne"
    },
    {
      "name": "Alice Hervieu"
    },
    {
      "name": "Lenaig Mescam-Mancini"
    },
    {
      "name": "François Bertucci"
    },
    {
      "name": "Juliette Beaujot"
    },
    {
      "name": "Thomas Ryckewaert"
    },
    {
      "name": "Philippe Rochaix"
    },
    {
      "name": "Thibaud Valentin"
    },
    {
      "name": "Nicolas Macagno"
    },
    {
      "name": "Florence Duffaud"
    },
    {
      "name": "Matthias Tallegas"
    },
    {
      "name": "Bruno Chetaille"
    },
    {
      "name": "Isabelle Valo"
    },
    {
      "name": "Emmanuelle Bompas"
    },
    {
      "name": "Marick Laé"
    },
    {
      "name": "Flore Delalande"
    },
    {
      "name": "Francisco Llamas Gutierrez"
    },
    {
      "name": "Nathalie Rioux-Leclercq"
    },
    {
      "name": "Jean-Yves Blay"
    },
    {
      "name": "Jean-Emmanuel Kurtz"
    },
    {
      "name": "Gabriel G. Malouf"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1hev7q98hsv48.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-74545-4",
  "fulltext_url": null,
  "id": "1hev7q98hsv48",
  "issns": [
    "2041-1723",
    "2041-1723"
  ],
  "landing_url": "https://hal.science/hal-05675887v1",
  "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": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "hal",
      "1.sdv.bbm"
    ],
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      "hal",
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    [
      "hal",
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    [
      "openalex",
      "2737|Tuberous Sclerosis Complex Research"
    ]
  ],
  "openalex": "W7165516045",
  "pdf_url": "https://hal.science/hal-05675887/document",
  "pmcid": null,
  "pmid": "42331846",
  "published": "2026-10-14",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/1hev7q98hsv48.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:57Z",
      "native_id": "hal-05675887",
      "source": "hal",
      "url": "https://hal.science/hal-05675887v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "hal:2.sdv.bbm.gtp",
      "subfield": "proteomics-metabolomics"
    },
    {
      "field": "biology",
      "origin": "hal:1.sdv.gen",
      "subfield": "genetics-genomics"
    },
    {
      "field": "medicine",
      "origin": "hal:2.sdv.gen.gh",
      "subfield": "human-genetics"
    },
    {
      "field": "medicine",
      "origin": "hal:1.sdv.can",
      "subfield": "oncology"
    }
  ],
  "title": "MiT fusions, TSC1–TSC2 divergence, and stem-like programs reveal distinct origins and vulnerabilities in PEComa",
  "title_text": "MiT fusions, TSC1–TSC2 divergence, and stem-like programs reveal distinct origins and vulnerabilities in PEComa",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:57Z",
  "url": "https://research.draconitic.com/paper/1hev7q98hsv48",
  "venue": "Nature Communications",
  "versions": []
}