Evidence map›Paper›PMID 35605606›Full record

ArticleNeuro-oncology2023

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

Dana Messinger, Micah K Harris, Jessica R Cummings, Chase Thomas, Tao Yang, Stefan R Sweha, Rinette Woo, Robert Siddaway, Martin Burkert, Stefanie Stallard and 28 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
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  3. Article
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  5. Article
  6. Article
  7. Article
  8. Molecular and Pathological Features of Paediatric High-Grade Gliomas.International journal of molecular sciences · 2024
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

38 authors at 11 institutions in 5 countries.

Dana MessingerDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Micah K HarrisDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Jessica R CummingsDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Chase ThomasDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Tao YangDepartment of Neurology, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Stefan R SwehaDepartment of Pathology, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Rinette WooCancer Research, California Pacific Medical Center Research Institute; San Francisco, California, USA.
Robert SiddawayArthur and Sonia Labatt Brain Tumour Research Centre and Division of Pathology, Hospital for Sick Children, Toronto, Canada.
Martin BurkertCentre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway.
Stefanie StallardDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Tingting QinDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Brendan MullanDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Ruby SiadaDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Ramya RavindranDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Michael NiculceaDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Abigail R DowlingDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Joshua BradinDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Kevin F GinnDepartment of Pediatrics, Children's Mercy Kansas City, Kansas City, Missouri, USA.
Melissa A H GenerDepartment of Pathology and Laboratory Medicine, Children's Mercy Kansas City, Kansas City, Missouri, USA.
Kathleen DorrisDepartment of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA.ORCID 0000-0003-0753-2176
Nicholas A VitanzaDepartment of Pediatrics, Seattle Children's, Seattle, Washington, USA.
Susanne V SchmidtInstitute of Innate Immunity, AG Immunogenomics, University Bonn, Bonn, Germany.
Jasper SpitzerInstitute of Innate Immunity, AG Immunogenomics, University Bonn, Bonn, Germany.
Jiang LiDana-Farber Boston Children's Cancer and Blood Disorders Center, Department of Pediatric Oncology, Boston, Massachusetts, USA.
Mariella G FilbinDana-Farber Boston Children's Cancer and Blood Disorders Center, Department of Pediatric Oncology, Boston, Massachusetts, USA.
Xuhong CaoDepartment of Pathology, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Maria G CastroDepartment of Neurosurgery, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Pedro R LowensteinDepartment of Neurosurgery, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Rajen ModyDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Arul ChinnaiyanDepartment of Pathology, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Pierre-Yves DesprezCancer Research, California Pacific Medical Center Research Institute; San Francisco, California, USA.
Sean McAllisterCancer Research, California Pacific Medical Center Research Institute; San Francisco, California, USA.
Matthew D DunCancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan NSW, Australia.
Cynthia HawkinsArthur and Sonia Labatt Brain Tumour Research Centre and Division of Pathology, Hospital for Sick Children, Toronto, Canada.
Sebastian M WaszakCentre for Molecular Medicine Norway (NCMM), Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway.
Sriram VennetiDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.
Carl KoschmannDivision of Pediatric Hematology-Oncology, Department of Pediatrics, University of Michigan Medical School (UMMS), Ann Arbor, Michigan, USA.ORCID 0000-0002-0825-7615
Viveka Nand YadavDepartment of Pediatrics at Children's Mercy Research Institute, Kansas City, Missouri, USA.
University of Michigan · USUniversity of California, San Francisco · USChildren's Mercy Hospital · USDana-Farber/Boston Children's Cancer and Blood Disorders Center · USHospital for Sick Children · CAOslo University Hospital · NOUniversity of Bonn · DEMercy Research · USSeattle Children's Hospital · USUniversity of Colorado Denver · USUniversity of Newcastle Australia · AU

Funding

Sequencing, Analysis, and Interpretation of SequencingUM1HG006508 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M, PIENTA, KENNETH J. · 2013 to 2016
$7.8M
Training Program in Tumor MicroenvironmentT32CA009676 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Maria G Castro, Analisa Virginia DiFeo · 1992 to 2026
$7.3M
Unravelling metabolic dependencies in H3K27M mutant DIPGR01NS110572 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Sriram Venneti · 2019 to 2026
$2.7M
Targeting EGFR/FOXG1-mediated resistance to ONC201 in H3K27M-mutant diffuse midline gliomaR01NS124607 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Carl J Koschmann · 2022 to 2026
$2.2M
The role of ATRX mutation in the epigenetic dysregulation of cell cycle in pediatric high-grade gliomaR01NS119231 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOSCHMANN, CARL J · 2021 to 2025
$1.9M
Targeting Breast Cancer Metastasis with Id1R44CA206723 · NCI · ORGANIX, INC. · PI MAHADEVAN, ANURADHA · 2016 to 2018
$1.7M
Targeting ATRX-Deficient Pediatric GBMK08NS099427 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KOSCHMANN, CARL J · 2017 to 2021
$811k
NCI NIH HHS R44 CA206723NCI NIH HHS T32 CA009676NHGRI NIH HHS UM1 HG006508NINDS NIH HHS K08 NS099427NINDS NIH HHS R01 NS110572NINDS NIH HHS R01 NS119231NINDS NIH HHS R01 NS124607
6 · The paper itself

Abstract

backgroundDiffuse 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.

methodsWhole 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.

resultsIncreased 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.

conclusionsH3K27M-mediated re-activation of ID1 in DMG results in a SPARCL1+ migratory transcriptional program that is therapeutically targetable with CBD.

Indexed as

Brain NeoplasmsGliomaAnimalsBrainCalcium-Binding ProteinsExtracellular Matrix ProteinsHistonesHumansInhibitor of Differentiation Protein 1MiceMutationSignal TransductionCalcium-Binding ProteinsExtracellular Matrix ProteinsHistonesID1 protein, humanIdb1 protein, mouseInhibitor of Differentiation Protein 1Sparcl1 protein, mouseCBDDMGID1invasion/migrationROS

Identifiers

PMID35605606
PMCPMC9825316
OpenAlexW4281382214

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.