A PROGNOSTIC HUMAN BRAIN NETWORK FOR DIFFUSE MIDLINE GLIOMA
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Le résumé fourni par la source
Abstract AIMS Diffuse midline glioma (DMG) are near-universally lethal tumours of the paediatric central nervous system. In animal models, DMG form brain-wide, integrated networks through neuron-to-glioma synapses and glioma- to-glioma gap junctional coupling. This extensive connectivity robustly promotes DMG growth and inva- sion through paracrine mechanisms and direct, neuron-to-glioma synapses. The organisation and clinical im- plications of these connections in the living human brain, however, remain to be elucidated. METHODS We leverage multimodal, real-world clinical data from 125 children with primary DMG (discovery dataset) and paediatric connectomic data (n=1000 children) to compute the brain-wide connectivity profile of DMG using lesion network mapping. RESULTS Pontine and thalamic DMG map to a unified brain network associated with patient short-term survival and defined by connectivity with the brainstem, cerebellum, limbic system, motor cortex, and insular cortex (DMG network; PFWE<0.01). Tumour connectivity with the DMG network was independently predictive of patient over- all survival in an external, multicentre validation cohort of 125 children with DMG (AUROC=0.95). Moreover, incidental surgical resection of thalamic DMG tissue with high connectivity to the DMG network conferred a significant survival advantage (P=0.02; median overall survival 9.2 vs. 30.5 months). Tumour growth pat- terns demonstrated directional tropism to DMG network connectivity peaks (Spearman’s ρ=0.54; PFWE=0.03). Orthogonal DMG network characterisation using multi-tracer positron emission tomography identified peak, in-network neurometabolic changes spatiotemporally aligned with the peak age incidence of DMG (R2=0.41) as well as dominant chemoarchitectural patterns of serotonergic, cholinergic, and noradrenergic signalling (R2adj=0.62). Finally, DMG with higher network-to-tumour connectivity exhibited epigenetic enrichment of pro- grammes promoting neurogenesis, neural stemness, and synaptic integration. CONCLUSION Collectively, these data provide real-world evidence for neural activity modulating DMG growth in humans, as previously described only in animal models, and are consistent with the hypothesis that DMG exploit otherwise healthy brain circuits to establish an environment that promotes tumour growth across multiple connectomic, neuromodulatory, and neurometabolic scales.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A prognostic human brain network for diffuse midline glioma
- Date Crossref
- 10/06/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Great Ormond Street Hospital Department of Histopathology pays non établi dans la noticeÉtablissement de santé
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University College London Developmental Biology and Cancer Section pays non établi dans la noticeUniversité ou école supérieure
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Queen Mary University of London pays non établi dans la noticeUniversité ou école supérieure
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CRUK Lung Cancer Centre of Excellence pays non établi dans la noticeStructure de recherche
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National Hospital for Neurology and Neurosurgery Victor Horsley Department of Neurosurgery pays non établi dans la noticeÉtablissement de santé
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Boston Children's Hospital Department of Neurology pays non établi dans la noticeÉtablissement de santé
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Harvard University Harvard Medical School pays non établi dans la noticeUniversité ou école supérieure
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Circuit Therapeutics (United States) pays non établi dans la noticeEntreprise
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Brigham and Women's Hospital Department of Neurology pays non établi dans la noticeÉtablissement de santé
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Great Ormond Street Hospital for Children NHS Foundation Trust pays non établi dans la noticeÉtablissement de santé
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Cancer Research UK pays non établi dans la noticeOrganisation à but non lucratif
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Universidad del Desarrollo pays non établi dans la noticeUniversité ou école supérieure
Department of Histopathology — Great Ormond Street Hospital, Developmental Biology and Cancer Section — University College London et Queen Mary University of London, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.