Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma.
Date
2024-07-15ICR Author
Author
Culliford, R
Lawrence, SED
Mills, C
Tippu, Z
Chubb, D
Cornish, AJ
Browning, L
Kinnersley, B
Bentham, R
Sud, A
Pallikonda, H
Renal Cancer Genomics England Consortium,
Frangou, A
Gruber, AJ
Litchfield, K
Wedge, D
Larkin, J
Turajlic, S
Houlston, RS
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Carcinoma, Renal Cell
Humans
Kidney Neoplasms
Whole Genome Sequencing
Mutation
Von Hippel-Lindau Tumor Suppressor Protein
Prognosis
Male
Female
DNA Copy Number Variations
Middle Aged
Epigenesis, Genetic
Aged
Gene Expression Regulation, Neoplastic
Immunotherapy
Research team
Cancer Genomics
Melanoma & Kidney Cancer
Language
eng
Date accepted
2024-06-17
License start date
2024-07-15
Citation
Nature Communications, 2024, 15 (1), pp. 5935 -
Publisher
NATURE PORTFOLIO