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.
Nature communications. 2024 Jul 15*** epublish ***
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, Renal Cancer Genomics England Consortium , Anna Frangou, Andreas J Gruber, Kevin Litchfield, David Wedge, James Larkin, Samra Turajlic, Richard S Houlston
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Renal and Skin Units, The Royal Marsden NHS Foundation Trust, London, UK., Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Department of Oncology, University College London Cancer Institute, London, UK., Nuffield Department of Medicine, Big Data Institute, University of Oxford, Oxford, UK., Department of Biology, University of Konstanz, Konstanz, Germany., Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Manchester Cancer Research Centre, University of Manchester, Manchester, UK., Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. .