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Genomic landscape of diffuse glioma revealed by whole genome sequencing

Author

Listed:
  • Ben Kinnersley

    (The Institute of Cancer Research
    UCL Cancer Institute)

  • Josephine Jung

    (Kings College London
    King’s College Hospital NHS Foundation Trust)

  • 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
    King’s College Hospital NHS Foundation Trust)

  • 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
    National Hospital for Neurology and Neurosurgery)

  • 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
    King’s College Hospital NHS Foundation Trust)

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.

Suggested Citation

  • 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 & Saf, 2025. "Genomic landscape of diffuse glioma revealed by whole genome sequencing," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59156-9
    DOI: 10.1038/s41467-025-59156-9
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    References listed on IDEAS

    as
    1. Moritz Gerstung & Clemency Jolly & Ignaty Leshchiner & Stefan C. Dentro & Santiago Gonzalez & Daniel Rosebrock & Thomas J. Mitchell & Yulia Rubanova & Pavana Anur & Kaixian Yu & Maxime Tarabichi & Ami, 2020. "The evolutionary history of 2,658 cancers," Nature, Nature, vol. 578(7793), pages 122-128, February.
    2. Yilong Li & Nicola D. Roberts & Jeremiah A. Wala & Ofer Shapira & Steven E. Schumacher & Kiran Kumar & Ekta Khurana & Sebastian Waszak & Jan O. Korbel & James E. Haber & Marcin Imielinski & Joachim We, 2020. "Patterns of somatic structural variation in human cancer genomes," Nature, Nature, vol. 578(7793), pages 112-121, February.
    3. Graham R. Bignell & Chris D. Greenman & Helen Davies & Adam P. Butler & Sarah Edkins & Jenny M. Andrews & Gemma Buck & Lina Chen & David Beare & Calli Latimer & Sara Widaa & Jonathon Hinton & Ciara Fa, 2010. "Signatures of mutation and selection in the cancer genome," Nature, Nature, vol. 463(7283), pages 893-898, February.
    4. Esther Rheinbay & Morten Muhlig Nielsen & Federico Abascal & Jeremiah A. Wala & Ofer Shapira & Grace Tiao & Henrik Hornshøj & Julian M. Hess & Randi Istrup Juul & Ziao Lin & Lars Feuerbach & Radhakris, 2020. "Analyses of non-coding somatic drivers in 2,658 cancer whole genomes," Nature, Nature, vol. 578(7793), pages 102-111, February.
    5. Ludmil B. Alexandrov & Jaegil Kim & Nicholas J. Haradhvala & Mi Ni Huang & Alvin Wei Tian Ng & Yang Wu & Arnoud Boot & Kyle R. Covington & Dmitry A. Gordenin & Erik N. Bergstrom & S. M. Ashiqul Islam , 2020. "The repertoire of mutational signatures in human cancer," Nature, Nature, vol. 578(7793), pages 94-101, February.
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