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Diffuse 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. Using lesion data from a total of 410 patients with high- and low-grade glioma, we identified – and replicated in an independent sample – three lesion covariance networks (LCNs), which reflect clusters of frequent glioma localization. These three LCNs overlapped with the anterior, posterior, and inferior horns of the lateral ventricles respectively, extending into the frontal, parietal, and temporal cortices. The first LCN, which overlapped with the anterior horn, was associated with low-grade, IDH-mutated/1p19q-codeleted tumors, as well as a neural transcriptomic signature and improved overall survival. Each LCN significantly coincided with multiple structural and functional connectivity networks, with LCN1 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 LCN. These results build upon prior reports of glioma growth along white matter pathways, as well as evidence for the coordination of glioma stem cell proliferation by neuronal activity. Cumulatively, our findings support a model wherein periventricular brain connectivity guides glioma development from the subventricular zone into distributed brain regions.

NIMG-31. PROPOSED ORIGINS AND PATHWAYS OF DIFFUSE GLIOMAS REVEALED BY LESION COVARIANCE NETWORKS