Transcriptomic and connectomic correlates of differential spatial patterning among gliomas.

ABSTRACT

Unravelling the complex events driving grade-specific spatial distribution of brain tumour occurrence requires rich datasets from both healthy individuals and patients. Here, we combined open-access data from The Cancer Genome Atlas, the UK Biobank and the Allen Brain Human Atlas to disentangle how the different spatial occurrences of glioblastoma multiforme and low-grade gliomas are linked to brain network features and the normative transcriptional profiles of brain regions. From MRI of brain tumour patients, we first constructed a grade-related frequency map of the regional occurrence of low-grade gliomas and the more aggressive glioblastoma multiforme. Using associated mRNA transcription data, we derived a set of differential gene expressions from glioblastoma multiforme and low-grade gliomas tissues of the same patients. By combining the resulting values with normative gene expressions from post-mortem brain tissue, we constructed a grade-related expression map indicating which brain regions express genes dysregulated in aggressive gliomas. Additionally, we derived an expression map of genes previously associated with tumour subtypes in a genome-wide association study (tumour-related genes). There were significant associations between grade-related frequency, grade-related expression and tumour-related expression maps, as well as functional brain network features (specifically, nodal strength and participation coefficient) that are implicated in neurological and psychiatric disorders. These findings identify brain network dynamics and transcriptomic signatures as key factors in regional vulnerability for glioblastoma multiforme and low-grade glioma occurrence, placing primary brain tumours within a well established framework of neurological and psychiatric cortical alterations.