{"entity": "publication", "iuid": "55a7b0bf4cb94d799662cb79f0cbfe84", "timestamp": "2026-09-23T22:37:30.194Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/55a7b0bf4cb94d799662cb79f0cbfe84.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/55a7b0bf4cb94d799662cb79f0cbfe84"}}, "title": "ARF suppression by MYC but not MYCN confers increased malignancy of aggressive pediatric brain tumors.", "authors": [{"family": "Mainwaring", "given": "Oliver J", "initials": "OJ", "orcid": "0000-0002-7973-9849", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/29515b9bedc74325aa50a0da62cd299a.json"}}, {"family": "Weishaupt", "given": "Holger", "initials": "H"}, {"family": "Zhao", "given": "Miao", "initials": "M", "orcid": "0000-0002-4895-1177", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/75b5d6dc5cde46b8aca859fb961bf1de.json"}}, {"family": "Ros\u00e9n", "given": "Gabriela", "initials": "G"}, {"family": "Borgenvik", "given": "Anna", "initials": "A"}, {"family": "Breinschmid", "given": "Laura", "initials": "L"}, {"family": "Verbaan", "given": "Annemieke D", "initials": "AD"}, {"family": "Richardson", "given": "Stacey", "initials": "S"}, {"family": "Thompson", "given": "Dean", "initials": "D"}, {"family": "Clifford", "given": "Steven C", "initials": "SC"}, {"family": "Hill", "given": "Rebecca M", "initials": "RM"}, {"family": "Annusver", "given": "Karl", "initials": "K", "orcid": "0000-0002-9515-7216", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/225d6f2d28a04cb1b47923316914bf0d.json"}}, {"family": "Sundstr\u00f6m", "given": "Anders", "initials": "A"}, {"family": "Holmberg", "given": "Karl O", "initials": "KO"}, {"family": "Kasper", "given": "Maria", "initials": "M", "orcid": "0000-0002-6117-2717", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a6accbbc62ab4b9eb2949d7c5d98c146.json"}}, {"family": "Hutter", "given": "Sonja", "initials": "S"}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/2e673fa8c86348fb8c1a2ae34ba7ba9a.json"}}], "type": "journal article", "published": "2023-03-03", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "14", "issue": "1", "pages": "1221", "issn-l": "2041-1723"}, "abstract": "Medulloblastoma, the most common malignant pediatric brain tumor, often harbors MYC amplifications. Compared to high-grade gliomas, MYC-amplified medulloblastomas often show increased photoreceptor activity and arise in the presence of a functional ARF/p53 suppressor pathway. Here, we generate an immunocompetent transgenic mouse model with regulatable MYC that develop clonal tumors that molecularly resemble photoreceptor-positive Group 3 medulloblastoma. Compared to MYCN-expressing brain tumors driven from the same promoter, pronounced ARF silencing is present in our MYC-expressing model and in human medulloblastoma. While partial Arf suppression causes increased malignancy in MYCN-expressing tumors, complete Arf depletion promotes photoreceptor-negative high-grade glioma formation. Computational models and clinical data further identify drugs targeting MYC-driven tumors with a suppressed but functional ARF pathway. We show that the HSP90 inhibitor, Onalespib, significantly targets MYC-driven but not MYCN-driven tumors in an ARF-dependent manner. The treatment increases cell death in synergy with cisplatin and demonstrates potential for targeting MYC-driven medulloblastoma.", "doi": "10.1038/s41467-023-36847-9", "pmid": "36869047", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC9984535"}, {"db": "pii", "key": "10.1038/s41467-023-36847-9"}], "notes": [], "created": "2026-09-23T11:04:01.417Z", "modified": "2026-09-23T11:04:01.582Z"}