Genomic landscape of diffuse glioma revealed by whole genome sequencing

Ben Kinnersley (), Josephine Jung (), Alex J. Cornish, Daniel Chubb, Ross Laxton, Anna Frangou, Andreas J. Gruber, Amit Sud, Giulio Caravagna, Andrea Sottoriva, David C. Wedge, Thomas Booth, Safa Al-Sarraj, Samuel E. D. Lawrence, Erminia Albanese, Giulio Anichini, David Baxter, Alexandros Boukas, Yasir A. Chowdhury, Pietro D’Urso, Robert Corns, Andrew Dapaah, Ellie Edlmann, Fay Greenway, Paul Grundy, Ciaran S. Hill, Michael D. Jenkinson, Sandhya Trichinopoly Krishna, Stuart Smith, Susruta Manivannan, Andrew J. Martin, Samir Matloob, Soumya Mukherjee, Kevin O’Neill, Puneet Plaha, Jonathan Pollock, Stephen Price, Ola Rominiyi, Bobby Sachdev, Fozia Saeed, Saurabh Sinha, Lewis Thorne, Ismail Ughratdar, Peter Whitfield, Amir Saam Youshani, Helen Bulbeck, Prabhu Arumugam, Richard Houlston () and Keyoumars Ashkan ()
Additional contact information
Ben Kinnersley: The Institute of Cancer Research
Josephine Jung: Kings College London
Alex J. Cornish: The Institute of Cancer Research
Daniel Chubb: The Institute of Cancer Research
Ross Laxton: King’s College Hospital NHS Foundation Trust
Anna Frangou: Nuffield Department of Medicine
Andreas J. Gruber: University of Konstanz
Amit Sud: The Institute of Cancer Research
Giulio Caravagna: The Institute of Cancer Research
Andrea Sottoriva: The Institute of Cancer Research
David C. Wedge: University of Manchester
Thomas Booth: St Thomas’s Hospital
Safa Al-Sarraj: King’s College Hospital NHS Foundation Trust
Samuel E. D. Lawrence: The Institute of Cancer Research
Erminia Albanese: Royal Stoke University Hospital
Giulio Anichini: Charing Cross Hospital, 3S corridor
David Baxter: Royal National Orthopaedic Hospital
Alexandros Boukas: John Radcliffe Hospital
Yasir A. Chowdhury: Queen Elizabeth Hospital Birmingham
Pietro D’Urso: Manchester Royal Infirmary
Robert Corns: Leeds General Infirmary
Andrew Dapaah: Queen’s Medical Centre NHS Trust
Ellie Edlmann: University Hospitals Plymouth NHS Trust
Fay Greenway: St. George’s University Hospitals NHS Foundation Trust
Paul Grundy: Southampton General Hospital
Ciaran S. Hill: UCL Cancer Institute
Michael D. Jenkinson: The Walton Centre NHS Foundation Trust
Sandhya Trichinopoly Krishna: The Walton Centre NHS Foundation Trust
Stuart Smith: Queen’s Medical Centre NHS Trust
Susruta Manivannan: Southampton General Hospital
Andrew J. Martin: St. George’s University Hospitals NHS Foundation Trust
Samir Matloob: Queen’s Hospital Romford
Soumya Mukherjee: Addenbrookes Hospital
Kevin O’Neill: Charing Cross Hospital, 3S corridor
Puneet Plaha: John Radcliffe Hospital
Jonathan Pollock: Queen’s Hospital Romford
Stephen Price: Addenbrookes Hospital
Ola Rominiyi: Royal Hallamshire Hospital
Bobby Sachdev: Royal Stoke University Hospital
Fozia Saeed: Leeds General Infirmary
Saurabh Sinha: Royal Hallamshire Hospital
Lewis Thorne: National Hospital for Neurology and Neurosurgery
Ismail Ughratdar: Queen Elizabeth Hospital Birmingham
Peter Whitfield: University Hospitals Plymouth NHS Trust
Amir Saam Youshani: Manchester Royal Infirmary
Helen Bulbeck: Brainstrust, 4 Yvery Court
Prabhu Arumugam: One Canada Square
Richard Houlston: The Institute of Cancer Research
Keyoumars Ashkan: Kings College London

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59156-9

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