Transcriptomic and connectomic correlates of differential spatial patterning among glioblastomas and low-grade gliomas

Abstract

SUMMARYBackgroundUnravelling 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 UKBiobank and the Allen Brain Human Atlas to disentangle how the different spatial occurrences of Glioblastoma Multiforme (GBM) and Low-Grade Gliomas (LGG) are linked to brain network features and the normative transcriptional profiles of brain regions.MethodsFrom MRI of brain tumour patients we first constructed a grade-related frequency map of the regional occurrence of LGG and the more aggressive GBM. Using associated mRNA transcription data, we derived a set of differential gene expressions from GBM and LGG tissues of the same patients. By combining the resulting values with normative gene expressions from postmortem 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 GWAS study (tumour-related genes).ResultsThere 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.ConclusionsThese findings identify brain network dynamics and transcriptomic signatures as key factors in regional vulnerability for GBM and LGG occurrence, placing primary brain tumours within a well-established framework of neurological and psychiatric cortical alterations.