ORCID

Abstract

Diffuse gliomas are the commonest malignant primary brain tumour in adults. Herein, we present analysis of the genomic landscape of adult glioma, by whole genome sequencing of 403 tumours (256 glioblastoma, 89 astrocytoma, 58 oligodendroglioma; 338 primary, 65 recurrence). We identify an extended catalogue of recurrent coding and non-coding genetic mutations that represents a source for future studies and provides a high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and extrachromosomal DNA. Finally, we relate these to clinical outcome. As well as identifying drug targets for treatment of glioma our findings offer the prospect of improving treatment allocation with established targeted therapies.

Publication Date

2025-05-07

Publication Title

Nature Communications

Volume

16

Issue

1

ISSN

2041-1723

Acceptance Date

2025-04-11

Deposit Date

2025-12-02

Funding

Funding was provided by the Wellcome Trust (214388), Cancer Research UK (C1298/A8362) and the Medical Research Council (R.H.). A.Sud and J.J. are in receipt of a National Institute for Health Research (NIHR) Academic Clinical Lectureship. A.Sud receives funding from the Royal Marsden Biomedical Research Centre, a starter grant for clinical lecturers from the Academy of Medical Sciences, and a Wellcome Trust Early Career Award (227000/Z/23/Z). This is a summary of independent research supported by the NIHR Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and the Institute of Cancer Research. B.K. would like to acknowledge funding from the UCL Dr Lori Houlihan Glioblastoma Fund and the National Brain Appeal. C.S.H. was supported by the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre. This research was made possible through access to data in the National Genomic Research Library, which is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The National Genomic Research Library holds data provided by patients and collected by the NHS as part of their care and data collected as part of their participation in research. The National Genomic Research Library is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. Curation of glioma clinical data was provided by Sophie T Williams.

Keywords

Adult, Aged, Astrocytoma/genetics, Brain Neoplasms/genetics, DNA Copy Number Variations, Female, Genome, Human, Genomics, Glioblastoma/genetics, Glioma/genetics, Humans, Male, Middle Aged, Mutation, Oligodendroglioma/genetics, Telomere/genetics, Whole Genome Sequencing

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