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Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma

Author

Listed:
  • Richard Culliford

    (The Institute of Cancer Research)

  • Samuel E. D. Lawrence

    (The Institute of Cancer Research)

  • Charlie Mills

    (The Institute of Cancer Research)

  • Zayd Tippu

    (The Royal Marsden NHS Foundation Trust
    The Institute of Cancer Research
    The Francis Crick Institute)

  • Daniel Chubb

    (The Institute of Cancer Research)

  • Alex J. Cornish

    (The Institute of Cancer Research)

  • Lisa Browning

    (Oxford University Hospitals NHS Foundation Trust)

  • Ben Kinnersley

    (The Institute of Cancer Research
    University College London Cancer Institute)

  • Robert Bentham

    (University College London Cancer Institute)

  • Amit Sud

    (The Institute of Cancer Research)

  • Husayn Pallikonda

    (The Royal Marsden NHS Foundation Trust
    The Institute of Cancer Research
    The Francis Crick Institute)

  • Anna Frangou

    (University of Oxford
    Max Planck Institute of Molecular Cell Biology and Genetics
    Centre for Systems Biology Dresden)

  • Andreas J. Gruber

    (University of Konstanz)

  • Kevin Litchfield

    (University College London Cancer Institute)

  • David Wedge

    (University of Manchester
    NIHR Manchester Biomedical Research Centre)

  • James Larkin

    (The Royal Marsden NHS Foundation Trust
    The Institute of Cancer Research)

  • Samra Turajlic

    (The Royal Marsden NHS Foundation Trust
    The Institute of Cancer Research
    The Francis Crick Institute)

  • Richard S. Houlston

    (The Institute of Cancer Research)

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common form of kidney cancer, but a comprehensive description of its genomic landscape is lacking. We report the whole genome sequencing of 778 ccRCC patients enrolled in the 100,000 Genomes Project, providing for a detailed description of the somatic mutational landscape of ccRCC. We identify candidate driver genes, which as well as emphasising the major role of epigenetic regulation in ccRCC highlight additional biological pathways extending opportunities for therapeutic interventions. Genomic characterisation identified patients with divergent clinical outcome; higher number of structural copy number alterations associated with poorer prognosis, whereas VHL mutations were independently associated with a better prognosis. The observations that higher T-cell infiltration is associated with better overall survival and that genetically predicted immune evasion is not common supports the rationale for immunotherapy. These findings should inform personalised surveillance and treatment strategies for ccRCC patients.

Suggested Citation

  • Richard Culliford & Samuel E. D. Lawrence & Charlie Mills & Zayd Tippu & Daniel Chubb & Alex J. Cornish & Lisa Browning & Ben Kinnersley & Robert Bentham & Amit Sud & Husayn Pallikonda & Anna Frangou , 2024. "Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49692-1
    DOI: 10.1038/s41467-024-49692-1
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