Evidence map›Paper›PMID 40298030›Full record

ArticleBrain : a journal of neurology2025

Disruption of DNA methylation underpins the neuroinflammation induced by targeted CNS radiotherapy.

Thomas O Millner, Pratistha Panday, Yunchen Xiao, James G Nicholson, James R Boot, Zsharmaine Arpe, Paul A Stevens, Nadia N Rahman, Xinyu Zhang, Charles Mein and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Thomas O MillnerBlizard Institute, Queen Mary University of London, London E1 2AT, UK.
Pratistha PandayBlizard Institute, Queen Mary University of London, London E1 2AT, UK.
Yunchen XiaoBlizard Institute, Queen Mary University of London, London E1 2AT, UK.
James G NicholsonBlizard Institute, Queen Mary University of London, London E1 2AT, UK.
James R BootBlizard Institute, Queen Mary University of London, London E1 2AT, UK.
Zsharmaine ArpeNational Hospital for Neurology and Neurosurgery, UCLH NHS Trust, London WC1N 3BG, UK.
Paul A StevensBlizard Institute, Queen Mary University of London, London E1 2AT, UK.
Nadia N RahmanBarts Cancer Institute, Queen Mary University of London, London EC1M 6AU, UK.
Xinyu ZhangBlizard Institute, Queen Mary University of London, London E1 2AT, UK.
Charles MeinBlizard Institute, Queen Mary University of London, London E1 2AT, UK.
Neil KitchenNational Hospital for Neurology and Neurosurgery, UCLH NHS Trust, London WC1N 3BG, UK.
Andrew W McEvoyNational Hospital for Neurology and Neurosurgery, UCLH NHS Trust, London WC1N 3BG, UK.
Edward McKintoshBarts Brain Tumour Centre, Barts Health NHS Trust, London E1 1BB, UK.
Grainne S McKennaBarts Brain Tumour Centre, Barts Health NHS Trust, London E1 1BB, UK.
Dimitrios ParaskevopoulosBlizard Institute, Queen Mary University of London, London E1 2AT, UK.
Nicolae Radu ZabetBlizard Institute, Queen Mary University of London, London E1 2AT, UK.ORCID 0000-0001-9964-6271
Rachel LewisBarts Brain Tumour Centre, Barts Health NHS Trust, London E1 1BB, UK.
Sara BadodiBlizard Institute, Queen Mary University of London, London E1 2AT, UK.ORCID 0000-0002-8407-8336
Silvia MarinoBlizard Institute, Queen Mary University of London, London E1 2AT, UK.ORCID 0000-0002-9612-2883

Funding

Barts Charity MGU0447Brain Tumour ResearchCancer Research UK C23985/A29199National Institute of Health and Care Research CL-2019-19-001Pathological Society of Great Britain and Ireland JCLSG 1021 01
6 · The paper itself

Abstract

Targeted radiotherapy is integral to the increasing survival of cancer patients; however, it has significant side effects, the underlying cellular and molecular mechanisms of which are ill-defined. It is well documented that targeted radiotherapy induces epigenetic changes in neoplastic tissue, which impacts tumour evolution; however, whether epigenetic deregulation also occurs in the surrounding non-neoplastic tissue and contributes to the occurrence of side effects is unknown. We characterized the DNA methylome in a unique cohort of irradiated peri-lesional brain tissue samples and integrated it with gene expression analysis at the spatial level. We show differences in DNA methylation patterns in irradiated brain tissue and identify specific inflammatory micro-environmental niches and their regulatory neuropeptides after irradiation. Finally, we show in a cerebral organoid model, that the same neuropeptides are upregulated as well as similar DNA methylation alterations and disruption of the DNA methylation machinery, in keeping with the interpretation that epigenetic dysregulation plays a role in neurotoxicity, hence raising the possibility it could represent a novel target for the reduction of radiotherapy side effects.

Indexed as

BrainDNA MethylationNeuroinflammatory DiseasesAnimalsEpigenesis, GeneticFemaleHumansMaleDNA methylationepigeneticsneuroinflammationneuro-oncologyradiotherapyspatial transcriptomics

Identifiers

PMID40298030
PMCPMC12404709

What Socratic 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 Socratic graph.