Genomic landscape of diffuse glioma revealed by whole genome sequencing
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.
Authors
- Peter C. Whitfield (ORCID: https://orcid.org/0000-0003-0566-1820)
- Fozia Saeed (ORCID: https://orcid.org/0009-0001-1751-7052)
- Ross C. Laxton (ORCID: https://orcid.org/0000-0002-3164-1201)
- Thomas C. Booth (ORCID: https://orcid.org/0000-0003-0984-3998)
- David C. Wedge (ORCID: https://orcid.org/0000-0002-7572-3196)
- Josephine Jung (ORCID: https://orcid.org/0000-0002-0056-440X)
- Safa Al‐Sarraj (ORCID: https://orcid.org/0000-0002-6783-3571)
- Robert Corns (ORCID: https://orcid.org/0000-0002-9608-0839)
- Puneet Plaha (ORCID: https://orcid.org/0000-0003-3103-6359)
- Richard S. Houlston (ORCID: https://orcid.org/0000-0002-5268-0242)
- Amir Saam Youshani (ORCID: https://orcid.org/0000-0002-0256-3400)
- Andreas Gruber (ORCID: https://orcid.org/0000-0001-7664-4257)
- Fay Greenway (ORCID: https://orcid.org/0000-0002-2414-4901)
- Giulio Caravagna (ORCID: https://orcid.org/0000-0003-4240-3265)
- Jonathan Pollock (ORCID: https://orcid.org/0000-0002-4171-4849)
- Andrew J. Martin (ORCID: https://orcid.org/0000-0002-0050-3850)
- David Baxter (ORCID: https://orcid.org/0000-0003-4468-2069)
- Saurabh R. Sinha (ORCID: https://orcid.org/0000-0003-0305-6731)
- Helen Bulbeck (ORCID: https://orcid.org/0000-0002-6775-5251)
- Andrea Sottoriva (ORCID: https://orcid.org/0000-0001-6709-9533)
- Alexandros Boukas
- Alex J. Cornish (ORCID: https://orcid.org/0000-0002-3966-3501)
- Michael D. Jenkinson (ORCID: https://orcid.org/0000-0003-4587-2139)
- Ismail Ughratdar
- Lewis W. Thorne (ORCID: https://orcid.org/0000-0002-7692-0378)
- Giulio Anichini (ORCID: https://orcid.org/0000-0001-6608-3310)
- Susruta Manivannan (ORCID: https://orcid.org/0000-0001-5905-2073)
- Ellie Edlmann (ORCID: https://orcid.org/0000-0002-7253-9115)
- Ciaran Scott Hill (ORCID: https://orcid.org/0000-0002-4488-4034)
- Amit Sud (ORCID: https://orcid.org/0000-0002-6133-0164)
- Samir Matloob (ORCID: https://orcid.org/0000-0002-0823-9687)
- Erminia Albanese
- Sandhya Trichinopoly Krishna (ORCID: https://orcid.org/0000-0002-4535-8896)
- Andrew Dapaah
- Stuart Smith (ORCID: https://orcid.org/0000-0002-4556-2707)
- Pietro Ivo D’Urso (ORCID: https://orcid.org/0000-0002-8823-3938)
- Ben Kinnersley (ORCID: https://orcid.org/0000-0003-1783-6296)
- Ola Rominiyi (ORCID: https://orcid.org/0000-0002-9724-0224)
- Daniel Chubb (ORCID: https://orcid.org/0000-0002-3813-0981)
- Yasir A Chowdhury
- Anna Frangou (ORCID: https://orcid.org/0000-0001-6990-2756)
- Soumya Mukherjee (ORCID: https://orcid.org/0000-0001-6852-508X)
- Stephen John Price (ORCID: https://orcid.org/0000-0002-7535-3009)
- Prabhu Arumugam
- B. Sachdev (ORCID: https://orcid.org/0000-0003-1559-8378)
- Paul Grundy
- Kevin O’Neill
- Keyoumars Ashkan
- Samuel Lawrence (ORCID: https://orcid.org/0000-0001-5856-7032)
Institutions
- Leeds General Infirmary (GB)
- St Thomas' Hospital (GB)
- Institute of Cancer Research (GB)
- University of Liverpool (GB)
- King's College - North Carolina (US)
- King's College London (GB)
- University of Konstanz (DE)
- Queen Elizabeth Hospital Birmingham (GB)
- Royal Stoke University Hospital (GB)
- St George’s University Hospitals NHS Foundation Trust (GB)
- Cancer Research UK (GB)
- Southampton General Hospital (GB)
- Isle of Wight NHS Trust (GB)
- Royal Hallamshire Hospital (GB)
- Manchester Royal Infirmary (GB)
- Charing Cross Hospital (GB)
- John Radcliffe Hospital (GB)
- Royal National Orthopaedic Hospital (GB)
- Walton Centre (GB)
- Sheffield Teaching Hospitals NHS Foundation Trust (GB)
- Evolutionary Genomics (United States) (US)
- King's College Hospital NHS Foundation Trust (GB)
- Queen's Hospital (GB)
- Cancer Research UK Manchester Institute (GB)
- Queen's Medical Centre (GB)
- Genomics England (GB)
- CRUK Lung Cancer Centre of Excellence (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- Addenbrooke's Hospital (GB)
- University Hospitals Plymouth NHS Trust (GB)
- University College London (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-07
- DOI
- https://doi.org/10.1038/s41467-025-59156-9
- Citations
- 4
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 6.50
Funders
- Wellcome Trust
- Royal Marsden NHS Foundation Trust
- Cancer Research UK
- National Institute for Health and Care Research
- Department of Health and Social Care
- University College London
- Medical Research Council