Evidence map›Paper›PMID 36070144›Full record

ArticleActa neuropathologica2022

Oncohistone interactome profiling uncovers contrasting oncogenic mechanisms and identifies potential therapeutic targets in high grade glioma.

Robert Siddaway, Laura Canty, Sanja Pajovic, Scott Milos, Etienne Coyaud, Stefanie-Grace Sbergio, Arun Kumaran Vadivel Anguraj, Evan Lubanszky, Hwa Young Yun, Alessia Portante and 6 more

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

Article in Acta neuropathologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Molecular and Pathological Features of Paediatric High-Grade Gliomas.International journal of molecular sciences · 2024
    Review
  10. Article
  11. Article
  12. Review
  13. Histone mutations in cancer.Biochemical Society transactions · 2023
    Article
  14. Review
  15. Article
  16. Targeting SWI/SNF ATPases in H3.3K27M diffuse intrinsic pontine gliomas.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  17. Review
  18. Review
  19. Article
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

16 authors at 3 institutions in 3 countries.

Robert SiddawayThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.
Laura CantyThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.
Sanja PajovicThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.
Scott MilosThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.
Etienne CoyaudPrincess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, ON, M5G 1L7, Canada.
Stefanie-Grace SbergioThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.
Arun Kumaran Vadivel AngurajThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.
Evan LubanszkyThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.
Hwa Young YunDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Alessia PortanteThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.
Sheyenne CaretteThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.
Cunjie ZhangCell Biology Program, Hospital for Sick Children, Toronto, ON, Canada.
Michael F MoranCell Biology Program, Hospital for Sick Children, Toronto, ON, Canada.
Brian RaughtPrincess Margaret Cancer Centre, University Health Network, 101 College Street, Toronto, ON, M5G 1L7, Canada.
Eric I CamposGenetics & Genome Biology Program, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada.
Cynthia HawkinsThe Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada. cynthia.hawkins@sickkids.ca.ORCID 0000-0003-2618-4402
Hospital for Sick Children · CAUniversity of Toronto · CAUniversity Health Network · CA

Funding

CIHR PJT-156407CIHR PJT-159683
6 · The paper itself

Abstract

Histone H3 mutations at amino acids 27 (H3K27M) and 34 (H3G34R) are recurrent drivers of pediatric-type high-grade glioma (pHGG). H3K27M mutations lead to global disruption of H3K27me3 through dominant negative PRC2 inhibition, while H3G34R mutations lead to local losses of H3K36me3 through inhibition of SETD2. However, their broader oncogenic mechanisms remain unclear. We characterized the H3.1K27M, H3.3K27M and H3.3G34R interactomes, finding that H3K27M is associated with epigenetic and transcription factor changes; in contrast H3G34R removes a break on cryptic transcription, limits DNA methyltransferase access, and alters mitochondrial metabolism. All 3 mutants had altered interactions with DNA repair proteins and H3K9 methyltransferases. H3K9me3 was reduced in H3K27M-containing nucleosomes, and cis-H3K9 methylation was required for H3K27M to exert its effect on global H3K27me3. H3K9 methyltransferase inhibition was lethal to H3.1K27M, H3.3K27M and H3.3G34R pHGG cells, underscoring the importance of H3K9 methylation for oncohistone-mutant gliomas and suggesting it as an attractive therapeutic target.

Indexed as

GliomaHistonesAmino AcidsChildDNAHumansMutationNucleosomesTranscription FactorsAmino AcidsDNAHistonesNucleosomesTranscription FactorsH3G34RH3K27MH3K9 methylationpHGG

Identifiers

PMID36070144
PMCPMC9547787
OpenAlexW4295013567

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.