Therapeutic targeting of prenatal pontine ID1 signaling in diffuse midline glioma.

Autor:	Messinger D; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Harris MK; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Cummings JR; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Thomas C; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Yang T; Department of Neurology, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Sweha SR; Department of Pathology, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Woo R; Cancer Research, California Pacific Medical Center Research Institute; San Francisco, California, USA., Siddaway R; Arthur and Sonia Labatt Brain Tumour Research Centre and Division of Pathology, Hospital for Sick Children, Toronto, Canada., Burkert M; Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway., Stallard S; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Qin T; Department of Computational Medicine and Bioinformatics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.; Rogel Cancer Center, University of Michigan, Ann Arbor, USA., Mullan B; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Siada R; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Ravindran R; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Niculcea M; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Dowling AR; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Bradin J; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Ginn KF; Department of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA., Gener MAH; Department of Pathology and Laboratory Medicine, Children's Mercy Kansas City, Kansas City, Missouri, USA., Dorris K; Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA., Vitanza NA; Department of Pediatrics, Seattle Children's, Seattle, Washington, USA., Schmidt SV; Institute of Innate Immunity, AG Immunogenomics, University Bonn, Bonn, Germany., Spitzer J; Institute of Innate Immunity, AG Immunogenomics, University Bonn, Bonn, Germany., Li J; Dana-Farber Boston Children's Cancer and Blood Disorders Center, Department of Pediatric Oncology, Boston, Massachusetts, USA., Filbin MG; Dana-Farber Boston Children's Cancer and Blood Disorders Center, Department of Pediatric Oncology, Boston, Massachusetts, USA., Cao X; Department of Pathology, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Castro MG; Department of Neurosurgery, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Lowenstein PR; Department of Neurosurgery, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.; Department of Cell and Developmental Biology, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Mody R; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Chinnaiyan A; Department of Pathology, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Desprez PY; Cancer Research, California Pacific Medical Center Research Institute; San Francisco, California, USA., McAllister S; Cancer Research, California Pacific Medical Center Research Institute; San Francisco, California, USA., Dun MD; Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan NSW, Australia., Hawkins C; Arthur and Sonia Labatt Brain Tumour Research Centre and Division of Pathology, Hospital for Sick Children, Toronto, Canada., Waszak SM; Centre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway.; Division of Pediatric and Adolescent Medicine, Department of Pediatric Research, Rikshospitalet, Oslo University Hospital, Oslo, Norway., Venneti S; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Koschmann C; Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA., Yadav VN; Department of Pediatrics at Children's Mercy Research Institute, Kansas City, Missouri, USA.
Jazyk:	angličtina
Zdroj:	Neuro-oncology [Neuro Oncol] 2023 Jan 05; Vol. 25 (1), pp. 54-67.
DOI:	10.1093/neuonc/noac141
Abstrakt:	Background: Diffuse midline gliomas (DMG) are highly invasive brain tumors with rare survival beyond two years past diagnosis and limited understanding of the mechanism behind tumor invasion. Previous reports demonstrate upregulation of the protein ID1 with H3K27M and ACVR1 mutations in DMG, but this has not been confirmed in human tumors or therapeutically targeted. Methods: Whole exome, RNA, and ChIP-sequencing was performed on the ID1 locus in DMG tissue. Scratch-assay migration and transwell invasion assays of cultured cells were performed following shRNA-mediated ID1-knockdown. In vitro and in vivo genetic and pharmacologic [cannabidiol (CBD)] inhibition of ID1 on DMG tumor growth was assessed. Patient-reported CBD dosing information was collected. Results: Increased ID1 expression in human DMG and in utero electroporation (IUE) murine tumors is associated with H3K27M mutation and brainstem location. ChIP-sequencing indicates ID1 regulatory regions are epigenetically active in human H3K27M-DMG tumors and prenatal pontine cells. Higher ID1-expressing astrocyte-like DMG cells share a transcriptional program with oligo/astrocyte-precursor cells (OAPCs) from the developing human brain and demonstrate upregulation of the migration regulatory protein SPARCL1. Genetic and pharmacologic (CBD) suppression of ID1 decreases tumor cell invasion/migration and tumor growth in H3.3/H3.1K27M PPK-IUE and human DIPGXIIIP* in vivo models of pHGG. The effect of CBD on cell proliferation appears to be non-ID1 mediated. Finally, we collected patient-reported CBD treatment data, finding that a clinical trial to standardize dosing may be beneficial. Conclusions: H3K27M-mediated re-activation of ID1 in DMG results in a SPARCL1+ migratory transcriptional program that is therapeutically targetable with CBD. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
Databáze:	MEDLINE
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