Abstract
For decades, it has been known that gliomas follow a non-random spatial distribution, appearing more often in some brain regions (e.g. the insula) compared to others (e.g. the occipital lobe). A better understanding of the localization patterns of gliomas could provide clues to the origins of these types of tumours, and consequently inform treatment targets. Following hypotheses derived from prior research into neuropsychiatric disease and cancer, gliomas may be expected to localize to brain regions characterized by functional 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 tumour 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 putative cells of origin for glioma, neural stem cells and oligodendrocyte precursor cells, exhibited a high glioma frequency. Leveraging a human brain atlas of post-mortem gene expression, we found that gliomas were localized to brain regions enriched with expression of genes associated with chromatin organization and synaptic signalling. A set of glioma proto-oncogenes was enriched among the transcriptomic correlates of glioma distribution. Finally, a regression model incorporating connectomic, cellular, and genetic factors explained 58% of the variance in glioma frequency. These results add to previous literature reporting the vulnerability of hub regions to neurological disease, as well as provide support for cancer stem cell theories of glioma. Our findings illustrate how factors of diverse scale, from genetic to connectomic, can independently influence the anatomic localization of brain dysfunction.
Highlights
Tumour location represents one of the most important prognostic factors for patients suffering from primary brain cancers (Jeremic et al, 1994; Sagberg et al, 2019), yet little is known about the mechanisms that determine the spatial distribution of gliomas across the brain.The importance of glioma location for diagnosis and treatment has been recognized since Percival Bailey and Harvey Cushing’s seminal classification of brain tumours in the earlyReceived April 21, 2020
To determine how different measures of biological contributions to glioma risk interrelated, we developed a multiple linear regression model combining each of the factors we found to be associated with tumour frequency
Consistent with prior reports, gliomas were rare in the occipital lobe, but relatively common in the insular cortex (Fig. 1B and Supplementary Table 1)
Summary
Tumour location represents one of the most important prognostic factors for patients suffering from primary brain cancers (Jeremic et al, 1994; Sagberg et al, 2019), yet little is known about the mechanisms that determine the spatial distribution of gliomas across the brain.The importance of glioma location for diagnosis and treatment has been recognized since Percival Bailey and Harvey Cushing’s seminal classification of brain tumours in the earlyReceived April 21, 2020. Tumour location represents one of the most important prognostic factors for patients suffering from primary brain cancers (Jeremic et al, 1994; Sagberg et al, 2019), yet little is known about the mechanisms that determine the spatial distribution of gliomas across the brain. The importance of glioma location for diagnosis and treatment has been recognized since Percival Bailey and Harvey Cushing’s seminal classification of brain tumours in the early.
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