Evidence map›Paper›PMID 38066546›Full record

ArticleGenome biology2023

Pediatric glioma histone H3.3 K27M/G34R mutations drive abnormalities in PML nuclear bodies.

Hsiao P J Voon, Linda Hii, Andrew Garvie, Maheshi Udugama, Brian Krug, Caterina Russo, Anderly C Chüeh, Roger J Daly, Alison Morey, Toby D M Bell and 8 more

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

Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

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  13. SAGE open medical case reports · 2024
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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

18 authors at 7 institutions in 4 countries.

Hsiao P J VoonCancer Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Linda HiiCancer Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Andrew GarvieCancer Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Maheshi UdugamaCancer Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Brian KrugDepartment of Human Genetics, McGill University, Montreal, QC, Canada.
Caterina RussoDepartment of Human Genetics, McGill University, Montreal, QC, Canada.
Anderly C ChüehCancer Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Roger J DalyCancer Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Alison MoreyDepartment of Microbiology, Monash University, Clayton, VIC, Australia.
Toby D M BellSchool of Chemistry, Monash University, Clayton, VIC, Australia.
Stephen J TurnerDepartment of Microbiology, Monash University, Clayton, VIC, Australia.
Joseph RosenbluhCancer Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia.
Paul DanielHudson Institute of Medical Research, Clayton, VIC, Australia.
Ron FiresteinHudson Institute of Medical Research, Clayton, VIC, Australia.
Jeffrey R MannDepartment of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
Philippe CollasDepartment of Molecular Medicine, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0317, Oslo, Norway.
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, QC, Canada.
Lee H WongCancer Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Australia. lee.wong@monash.edu.ORCID 0000-0002-4005-7330
Australian Regenerative Medicine Institute · AUMonash University · AUHudson Institute of Medical Research · AUMcGill University · CADiscovery Institute · USMcGill University Health Centre · CAOslo University Hospital · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPoint mutations in histone variant H3.3 (H3.3K27M, H3.3G34R) and the H3.3-specific ATRX/DAXX chaperone complex are frequent events in pediatric gliomas. These H3.3 point mutations affect many chromatin modifications but the exact oncogenic mechanisms are currently unclear. Histone H3.3 is known to localize to nuclear compartments known as promyelocytic leukemia (PML) nuclear bodies, which are frequently mutated and confirmed as oncogenic drivers in acute promyelocytic leukemia.

resultsWe find that the pediatric glioma-associated H3.3 point mutations disrupt the formation of PML nuclear bodies and this prevents differentiation down glial lineages. Similar to leukemias driven by PML mutations, H3.3-mutated glioma cells are sensitive to drugs that target PML bodies. We also find that point mutations in IDH1/2-which are common events in adult gliomas and myeloid leukemias-also disrupt the formation of PML bodies.

conclusionsWe identify PML as a contributor to oncogenesis in a subset of gliomas and show that targeting PML bodies is effective in treating these H3.3-mutated pediatric gliomas.

Indexed as

Brain NeoplasmsGliomaHistonesAdultChildHumansMutationPromyelocytic Leukemia Nuclear BodiesH3-3A protein, humanH3f3a protein, mouseHistonesArsenic trioxideHistone variant H3.3Pediatric gliomaPML bodies

Identifiers

PMID38066546
PMCPMC10704828
OpenAlexW4389486607

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.