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dc.contributor.authorMandal, Ayan S
dc.contributor.authorRomero-Garcia, Rafael
dc.contributor.authorSeidlitz, Jakob
dc.contributor.authorHart, Michael G
dc.contributor.authorAlexander-Bloch, Aaron F
dc.contributor.authorSuckling, John
dc.date.accessioned2022-01-28T16:43:17Z
dc.date.available2022-01-28T16:43:17Z
dc.date.issued2021
dc.identifier.issn2632-1297
dc.identifier.other34917940
dc.identifier.otherPMC8669792
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/333269
dc.description.abstractDiffuse gliomas have been hypothesized to originate from neural stem cells in the subventricular zone and develop along previously healthy brain networks. Here, we evaluated these hypotheses by mapping independent sources of glioma localization and determining their relationships with neurogenic niches, genetic markers and large-scale connectivity networks. By applying independent component analysis to lesion data from 242 adult patients with high- and low-grade glioma, we identified three lesion covariance networks, which reflect clusters of frequent glioma localization. Replicability of the lesion covariance networks was assessed in an independent sample of 168 glioma patients. We related the lesion covariance networks to important clinical variables, including tumour grade and patient survival, as well as genomic information such as molecular genetic subtype and bulk transcriptomic profiles. Finally, we systematically cross-correlated the lesion covariance networks with structural and functional connectivity networks derived from neuroimaging data of over 4000 healthy UK BioBank participants to uncover intrinsic brain networks that may that underlie tumour development. The three lesion covariance networks overlapped with the anterior, posterior and inferior horns of the lateral ventricles respectively, extending into the frontal, parietal and temporal cortices. These locations were independently replicated. The first lesion covariance network, which overlapped with the anterior horn, was associated with low-grade, isocitrate dehydrogenase -mutated/1p19q-codeleted tumours, as well as a neural transcriptomic signature and improved overall survival. Each lesion covariance network significantly coincided with multiple structural and functional connectivity networks, with the first bearing an especially strong relationship with brain connectivity, consistent with its neural transcriptomic profile. Finally, we identified subcortical, periventricular structures with functional connectivity patterns to the cortex that significantly matched each lesion covariance network. In conclusion, we demonstrated replicable patterns of glioma localization with clinical relevance and spatial correspondence with large-scale functional and structural connectivity networks. These results are consistent with prior reports of glioma growth along white matter pathways, as well as evidence for the coordination of glioma stem cell proliferation by neuronal activity. Our findings describe how the locations of gliomas relate to their proposed subventricular origins, suggesting a model wherein periventricular brain connectivity guides tumour development.
dc.languageeng
dc.publisherOxford University Press (OUP)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101755125
dc.sourceessn: 2632-1297
dc.subjectNeural stem cells
dc.subjectGlioma
dc.subjectsubventricular zone
dc.subjectFunctional Connectivity
dc.subjectStructural Connectivity
dc.titleLesion covariance networks reveal proposed origins and pathways of diffuse gliomas.
dc.typeArticle
dc.date.updated2022-01-28T16:43:16Z
prism.issueIdentifier4
prism.publicationNameBrain Commun
prism.volume3
dc.identifier.doi10.17863/CAM.80692
dcterms.dateAccepted2021-10-25
rioxxterms.versionofrecord10.1093/braincomms/fcab289
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidMandal, Ayan S [0000-0002-0780-3864]
dc.contributor.orcidSuckling, John [0000-0002-5098-1527]
dc.identifier.eissn2632-1297
pubs.funder-project-idMedical Research Council (MR/M009041/1)
cam.issuedOnline2021-12-04


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International