Journal article
Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 2.5MB, Terms of use)
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(Supplementary materials, zip, 7.7MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-024-49692-1
Authors
+ Melanoma Research Alliance
More from this funder
- Funder identifier:
- https://ror.org/025ck6r46
- Funding agency for:
- Turajlic, S
- Grant:
- 686061
+ National Institute of Health
More from this funder
- Funder identifier:
- https://ror.org/05h1kgg64
- Funding agency for:
- Turajlic, S
- Grant:
- U01 CA247439
+ United States Department of Defense
More from this funder
- Funder identifier:
- https://ror.org/0447fe631
- Funding agency for:
- Turajlic, S
- Grant:
- W81XWH-22-1-0652
+ Rosetrees Trust
More from this funder
- Funder identifier:
- https://ror.org/04e3zg361
- Funding agency for:
- Turajlic, S
- Grant:
- A2204
+ Ventana Research Corporation (United States)
More from this funder
- Funder identifier:
- https://ror.org/039tznx53
- Funding agency for:
- Turajlic, S
- Grant:
- 10467
- 10530
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 15
- Issue:
- 1
- Article number:
- 5935
- Publication date:
- 2024-07-15
- Acceptance date:
- 2024-06-17
- DOI:
- EISSN:
-
2041-1723
- ISSN:
-
2041-1723
- Language:
-
English
- Pubs id:
-
2015654
- Local pid:
-
pubs:2015654
- Source identifiers:
-
2111158
- Deposit date:
-
2024-07-15
- ARK identifier:
Terms of use
- Copyright holder:
- Culliford et al.
- Copyright date:
- 2024
- Rights statement:
- © The Author(s) 2024. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
- Licence:
- CC Attribution (CC BY)
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