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; Keyoumars Ashkan

doi:10.1038/s41467-025-59156-9

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'UrsoRobert 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, Keyoumars Ashkan

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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.

Original language	English
Article number	4233
Journal	Nature Communications
Volume	16
Issue number	1
Early online date	7 May 2025
DOIs	https://doi.org/10.1038/s41467-025-59156-9
Publication status	Published - 7 May 2025

Keywords

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

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10.1038/s41467-025-59156-9Licence: CC BY-NC-ND

Genomic landscape of diffuse glioma_KINNERSLEY_Accepted11April2025_GREEN_AAM (CC BY)Accepted author manuscript, 6.22 MBLicence: CC BY

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Kinnersley, B., Jung, J., Cornish, A. J., Chubb, D., Laxton, R., Frangou, A., Gruber, A. J., Sud, A., Caravagna, G., Sottoriva, A., Wedge, D. C., Booth, T., Al-Sarraj, S., Lawrence, S. E. D., Albanese, E., Anichini, G., Baxter, D., Boukas, A., Chowdhury, Y. A., ... Ashkan, K. (2025). Genomic landscape of diffuse glioma revealed by whole genome sequencing. Nature Communications, 16(1), Article 4233. https://doi.org/10.1038/s41467-025-59156-9

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title = "Genomic landscape of diffuse glioma revealed by whole genome sequencing",

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.",

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

author = "Ben Kinnersley and Josephine Jung and Cornish, {Alex J} and Daniel Chubb and Ross Laxton and Anna Frangou and Gruber, {Andreas J} and Amit Sud and Giulio Caravagna and Andrea Sottoriva and Wedge, {David C} and Thomas Booth and Safa Al-Sarraj and Lawrence, {Samuel E D} and Erminia Albanese and Giulio Anichini and David Baxter and Alexandros Boukas and Chowdhury, {Yasir A} and Pietro D'Urso and Robert Corns and Andrew Dapaah and Ellie Edlmann and Fay Greenway and Paul Grundy and Hill, {Ciaran S} and Jenkinson, {Michael D} and {Trichinopoly Krishna}, Sandhya and Stuart Smith and Susruta Manivannan and Martin, {Andrew J} and Samir Matloob and Soumya Mukherjee and Kevin O'Neill and Puneet Plaha and Jonathan Pollock and Stephen Price and Ola Rominiyi and Bobby Sachdev and Fozia Saeed and Saurabh Sinha and Lewis Thorne and Ismail Ughratdar and Peter Whitfield and Youshani, {Amir Saam} and Helen Bulbeck and Prabhu Arumugam and Richard Houlston and Keyoumars Ashkan",

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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 2025, 'Genomic landscape of diffuse glioma revealed by whole genome sequencing', Nature Communications, vol. 16, no. 1, 4233. https://doi.org/10.1038/s41467-025-59156-9

TY - JOUR

T1 - Genomic landscape of diffuse glioma revealed by whole genome sequencing

AU - Kinnersley, Ben

AU - Jung, Josephine

AU - Cornish, Alex J

AU - Chubb, Daniel

AU - Laxton, Ross

AU - Frangou, Anna

AU - Gruber, Andreas J

AU - Sud, Amit

AU - Caravagna, Giulio

AU - Sottoriva, Andrea

AU - Wedge, David C

AU - Booth, Thomas

AU - Al-Sarraj, Safa

AU - Lawrence, Samuel E D

AU - Albanese, Erminia

AU - Anichini, Giulio

AU - Baxter, David

AU - Boukas, Alexandros

AU - Chowdhury, Yasir A

AU - D'Urso, Pietro

AU - Corns, Robert

AU - Dapaah, Andrew

AU - Edlmann, Ellie

AU - Greenway, Fay

AU - Grundy, Paul

AU - Hill, Ciaran S

AU - Jenkinson, Michael D

AU - Trichinopoly Krishna, Sandhya

AU - Smith, Stuart

AU - Manivannan, Susruta

AU - Martin, Andrew J

AU - Matloob, Samir

AU - Mukherjee, Soumya

AU - O'Neill, Kevin

AU - Plaha, Puneet

AU - Pollock, Jonathan

AU - Price, Stephen

AU - Rominiyi, Ola

AU - Sachdev, Bobby

AU - Saeed, Fozia

AU - Sinha, Saurabh

AU - Thorne, Lewis

AU - Ughratdar, Ismail

AU - Whitfield, Peter

AU - Youshani, Amir Saam

AU - Bulbeck, Helen

AU - Arumugam, Prabhu

AU - Houlston, Richard

AU - Ashkan, Keyoumars

PY - 2025/5/7

Y1 - 2025/5/7

N2 - 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.

AB - 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.

KW - Humans

KW - Whole Genome Sequencing

KW - Brain Neoplasms/genetics

KW - Glioma/genetics

KW - Mutation

KW - DNA Copy Number Variations

KW - Adult

KW - Female

KW - Male

KW - Middle Aged

KW - Genomics

KW - Glioblastoma/genetics

KW - Aged

KW - Genome, Human

KW - Astrocytoma/genetics

KW - Oligodendroglioma/genetics

KW - Telomere/genetics

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U2 - 10.1038/s41467-025-59156-9

DO - 10.1038/s41467-025-59156-9

M3 - Article

C2 - 40335506

SN - 2041-1723

VL - 16

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4233

ER -

Genomic landscape of diffuse glioma revealed by whole genome sequencing

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