{
  "abstract": "SUMMARY: Many cancers are driven by mutationally altered transcription factors (TFs) that rewire cells to an oncogenic state. Cells must activate specific mechanisms to tolerate the burden of oncogenic TF activity. To define such mechanisms, we focused on a canonical oncogenic fusion protein-driven cancer, alveolar rhabdomyosarcoma (ARMS), where the PAX3::FOXO1 fusion protein hyperactivates and mislocalizes PAX3 and FOXO1 TF functions. Employing sequential functional genomic CRISPR-Cas9 screens, we identified FANCM, a DNA translocase in the Fanconi anemia pathway, as a selective dependency in PAX3::FOXO1+ ARMS. FANCM loss reduces fusion protein levels, induces myogenic differentiation, and disrupts the PAX3::FOXO1 transcriptional program, thereby halting oncogenic proliferation. Mechanistically, FANCM depletion exacerbates replication stress (RS) and DNA damage signaling, with chromatin-associated RS enriched at PAX3::FOXO1 target gene loci, resulting in selective downregulation of the oncogenic program. CRISPR exon-tiling screens prioritized FANCM’s helicase and DNA-binding domains as essential for this dependency, linking FANCM-mediated replication fork binding to sustained oncogenesis.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA",
    "INSERM UMR 944, IRSL, St Louis Hospital, University of Paris-Cité, Paris, France",
    "Broad Institute of MIT and Harvard, Cambridge, MA, USA",
    "Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA",
    "Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Christopher D. Delaney"
    },
    {
      "affs": [
        0
      ],
      "name": "Min Lu"
    },
    {
      "affs": [
        0
      ],
      "name": "Seth P. Zimmerman"
    },
    {
      "affs": [
        0
      ],
      "name": "Yingying Meng"
    },
    {
      "affs": [
        1
      ],
      "name": "Camille Vaganay"
    },
    {
      "affs": [
        0
      ],
      "name": "Christian G. Cerda-Smith"
    },
    {
      "affs": [
        0
      ],
      "name": "Annie Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Jacob P. Hoj"
    },
    {
      "affs": [
        0
      ],
      "name": "Shane T. Killarney"
    },
    {
      "affs": [
        0
      ],
      "name": "Kerry Dillon"
    },
    {
      "affs": [
        0
      ],
      "name": "Amy E. Stewart"
    },
    {
      "affs": [
        0
      ],
      "name": "Kevin Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Julia D. Caci"
    },
    {
      "affs": [
        0
      ],
      "name": "Olivia White"
    },
    {
      "affs": [
        1
      ],
      "name": "Alexandre Puissant"
    },
    {
      "affs": [
        2
      ],
      "name": "David E. Root"
    },
    {
      "affs": [
        3
      ],
      "name": "Jack F. Shern"
    },
    {
      "affs": [
        0
      ],
      "name": "Christine E. Eyler"
    },
    {
      "affs": [
        4
      ],
      "name": "Chun-Wei David Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Christopher M. Counter"
    },
    {
      "affs": [
        0
      ],
      "name": "Corinne M. Linardic"
    },
    {
      "affs": [
        0
      ],
      "name": "Lee Zou"
    },
    {
      "affs": [
        0
      ],
      "name": "Kris C. Wood"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c82q3g39tz3c7.bib",
  "cited_by": 0,
  "doi": "10.1016/j.celrep.2026.117960",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13728430/?tool=EBI",
  "id": "c82q3g39tz3c7",
  "issns": [
    "2211-1247"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13728430",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|Chromatin Remodeling and Cancer"
    ]
  ],
  "openalex": "W7211960441",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13728430/pdf/?tool=EBI",
  "pmcid": "PMC13728430",
  "pmid": "42715099",
  "published": "2026-09-08",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c82q3g39tz3c7.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:51Z",
      "native_id": "PMC:PMC13728430",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13728430"
    },
    {
      "first_seen": "2026-11-07T12:21:26Z",
      "native_id": "PMC13728430",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.celrep.2026.117960"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Chromatin Remodeling and Cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "FANCM is required for the PAX3::FOXO1-driven oncogenic program in rhabdomyosarcoma",
  "title_text": "FANCM is required for the PAX3::FOXO1-driven oncogenic program in rhabdomyosarcoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:26Z",
  "url": "https://research.draconitic.com/paper/c82q3g39tz3c7",
  "venue": "Cell reports",
  "versions": []
}