Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma.
Loading...
Embargo End Date
Authors
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
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
Document Type
Journal Article
Date
2024-07-15
Date Accepted
2024-06-17
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.
Citation
Nature Communications, 2024, 15 (1), pp. 5935 -
Rights
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
2041-1723
2041-1723
Collections
Research Team
Cancer Genomics
Melanoma & Kidney Cancer
Melanoma & Kidney Cancer