| Title: | A prognostic human brain network for diffuse midline glioma |
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| Authors: | ID Sidpra, Jai (Author)
ID Lind, Valentina (Author)
ID Cohen, Alexander L. (Author)
ID Schaper, Frederic L. W .V. J. (Author)
ID Stone, Thomas J (Author)
ID Grabovska, Yura (Author)
ID Biswas, Asthik (Author)
ID Sudhakar, Sniya (Author)
ID Sepulveda, Francisco (Author)
ID Peres, Bruno S. (Author)
ID Avsenik, Jernej (Author), et al. |
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| Files: |  PDF - Presentation file, download (77,26 MB)
MD5: 12116CB0BACA9F5F92B634E41A2D683B
 URL - Source URL, visit https://www.nature.com/articles/s41586-026-10631-3
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| Language: | English |
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| Typology: | 1.01 - Original Scientific Article |
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| Organization: |  UKC LJ - Ljubljana University Medical Centre
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| Abstract: | Diffuse midline gliomas (DMGs) are near-universally lethal tumours of the childhood central nervous system1,2. In animal models, DMGs form brain-wide integrated networks through neuron-to-glioma synapses3-6 and glioma-to-glioma gap junctional coupling3. This extensive connectivity robustly promotes the growth and invasion of DMG3-9 and other glial malignancies10-12 through paracrine mechanisms and direct neuron-to-glioma synapses. However, the organization and clinical implications of these connections in the living human brain remain to be elucidated. Here, we develop tumour network mapping to compute the brain-wide connectivity profile of DMG, defining a conserved brain network across pontine and thalamic DMG associated with patient short-term survival (DMG network). Tumour functional connectivity with the DMG network was independently predictive of patient overall survival across two external validation cohorts. Tumour growth mapped to DMG network-specific trajectories and peak in-network neurometabolic changes across development spatiotemporally aligned with the peak age incidence of DMG. Analyses of single-nucleus RNA sequencing data confirmed diverse synaptic gene enrichment in high-connectivity DMG. Strikingly, incidental surgical resection of high-connectivity thalamic DMG tissue conferred a significant survival advantage. Collectively, these data define a conserved and prognostically important brain network in children with DMG, consistent with the hypothesis that DMGs exploit otherwise healthy brain circuits to promote tumour growth. |
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| Keywords: | diffuse midline glioma, brain networks, prognosis, brain mapping |
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| Publication status: | Published |
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| Publication version: | Version of Record |
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| Year of publishing: | 2026 |
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| Number of pages: | str. 769-779 |
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| Numbering: | Vol. 655, issue 8123 |
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| PID: | 20.500.12556/DiRROS-31315  |
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| UDC: | 616.8-006 |
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| ISSN on article: | 1476-4687 |
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| DOI: | 10.1038/s41586-026-10631-3 |
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| COBISS.SI-ID: | 281328131 |
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| Note: | Nasl. z nasl. zaslona;
Opis vira z dne 19. 1. 2026;
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| Publication date in DiRROS: | 27.07.2026 |
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| Views: | 117 |
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| Downloads: | 70 |
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