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Transcriptomic and connectomic correlates of differential spatial patterning among gliomas.

Accepted version
Peer-reviewed

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Article

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Authors

Romero-Garcia, Rafael  ORCID logo  https://orcid.org/0000-0002-5199-4573
Bethlehem, Richard AI 
Crespo-Facorro, Benedicto 
Hart, Michael G 

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.

Description

Keywords

connectomic, gene expression, glioma, transcriptomic, Humans, Glioblastoma, Transcriptome, Genome-Wide Association Study, Connectome, Glioma, Brain Neoplasms

Journal Title

Brain

Conference Name

Journal ISSN

0006-8950
1460-2156

Volume Title

Publisher

Oxford University Press (OUP)
Sponsorship
Cancer Research UK (A25117)
National Institute for Health and Care Research (IS-BRC-1215-20014)
RRG is funded by a non-clinical post-doctoral Brain fellowship, the EMERGIA Junta de Andalucía program (EMERGIA20_00139) and Cancer Research UK Cambridge Centre (grant ref: A25117) and the Plan Propio of the University of Seville.