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

Autor: Culliford R; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Lawrence SED; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Mills C; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Tippu Z; Renal and Skin Units, The Royal Marsden NHS Foundation Trust, London, UK.; Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London, UK.; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK., Chubb D; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Cornish AJ; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Browning L; Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK., Kinnersley B; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK.; Department of Oncology, University College London Cancer Institute, London, UK., Bentham R; Department of Oncology, University College London Cancer Institute, London, UK., Sud A; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK., Pallikonda H; Renal and Skin Units, The Royal Marsden NHS Foundation Trust, London, UK.; Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London, UK.; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK., Frangou A; Nuffield Department of Medicine, Big Data Institute, University of Oxford, Oxford, UK.; Algebraic Systems Biology, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.; Algebraic Systems Biology, Centre for Systems Biology Dresden, Dresden, Germany., Gruber AJ; Department of Biology, University of Konstanz, Konstanz, Germany., Litchfield K; Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, London, UK., Wedge D; Manchester Cancer Research Centre, University of Manchester, Manchester, UK.; NIHR Manchester Biomedical Research Centre, Manchester, UK., Larkin J; Renal and Skin Units, The Royal Marsden NHS Foundation Trust, London, UK.; Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London, UK., Turajlic S; Renal and Skin Units, The Royal Marsden NHS Foundation Trust, London, UK.; Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London, UK.; Cancer Dynamics Laboratory, The Francis Crick Institute, London, UK., Houlston RS; Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK. richard.houlston@icr.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Jul 15; Vol. 15 (1), pp. 5935. Date of Electronic Publication: 2024 Jul 15.
DOI: 10.1038/s41467-024-49692-1
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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