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<p>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.</p>

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Genomic landscape of diffuse glioma revealed by whole genome sequencing

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年5月7日

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  • 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

摘要

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.