Genetic, Cellular, and Connectomic Characterization of the Adult Human Brain Regions Commonly Plagued by Glioma

A better understanding of the nonrandom localization patterns of gliomas across the brain could lend clues to the origins of these types of tumors. Following hypotheses derived from prior research into neuropsychiatric disease and cancer, gliomas may be expected to localize to brain regions characterized by hubness, stem-like cells, and transcription of genetic drivers of gliomagenesis. We combined neuroimaging data from 335 adult patients with high- and low-grade glioma to form a replicable tumor frequency map. Using this map, we demonstrated that glioma frequency is elevated in association cortex and correlated with multiple graph-theoretical metrics of high functional connectedness. Brain regions populated with stem-like cells also exhibited a high glioma frequency. Furthermore, gliomas were localized to brain regions enriched with the expression of genes associated with chromatin organization and synaptic signaling. Finally, a regression model incorporating connectomic, cellular, and genetic factors explained 58% of the variance in glioma frequency. Our findings illustrate how factors of diverse scale, from genetic to connectomic, can independently influence the anatomic localization of oncogenesis.