Genomic landscape of diffuse glioma revealed by whole genome sequencing
Kinnersley, Ben Jung, Josephine Cornish, Alex J Chubb, Daniel Laxton, Ross Frangou, Anna Gruber, Andreas J Sud, Amit Caravagna, Giulio Sottoriva, Andrea
Kinnersley, Ben
Jung, Josephine
Cornish, Alex J
Chubb, Daniel
Laxton, Ross
Frangou, Anna
Gruber, Andreas J
Sud, Amit
Caravagna, Giulio
Sottoriva, Andrea
Affiliation
Institute of Cancer Research; University College London; Kings College London; King's College Hospital NHS Foundation Trust; University of Oxford; University of Konstanz; University of Manchester; King's College London; Guy’s and St Thomas’ NHS Foundation Trust; University Hospitals of North Midlands NHS Trust; Imperial College Healthcare NHS Trust; Royal National Orthopaedic Hospital NHS Trust; Oxford University Hospitals NHS Foundation Trust; University Hospitals Birmingham NHS Foundation Trust; Manchester University NHS Foundation Trust; Leeds Teaching Hospitals NHS Trust; Queen's Medical Centre NHS Trust; University Hospitals Plymouth NHS Trust; St. George's University Hospitals NHS Foundation Trust; University Hospital Southampton NHS Foundation Trust; University College London Hospitals NHS Foundation Trust; Walton Centre NHS Foundation Trust; Barking, Havering and Redbridge University Hospitals NHS Trust; Cambridge University Hospitals NHS Foundation Trust; Sheffield Teaching Hospitals NHS Foundation Trust; Braintrust; Genomics England
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Publication date
2025-05-07
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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.
Citation
Kinnersley B, Jung J, Cornish AJ, Chubb D, Laxton R, Frangou A, Gruber AJ, Sud A, Caravagna G, Sottoriva A, Wedge DC, Booth T, Al-Sarraj S, Lawrence SED, Albanese E, Anichini G, Baxter D, Boukas A, Chowdhury YA, D'Urso P, Corns R, Dapaah A, Edlmann E, Greenway F, Grundy P, Hill CS, Jenkinson MD, Trichinopoly Krishna S, Smith S, Manivannan S, Martin AJ, Matloob S, Mukherjee S, O'Neill K, Plaha P, Pollock J, Price S, Rominiyi O, Sachdev B, Saeed F, Sinha S, Thorne L, Ughratdar I, Whitfield P, Youshani AS, Bulbeck H, Arumugam P, Houlston R, Ashkan K. Genomic landscape of diffuse glioma revealed by whole genome sequencing. Nat Commun. 2025 May 7;16(1):4233. doi: 10.1038/s41467-025-59156-9.
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Article