Whole genome sequencing refines stratification and therapy of patients with clear cell renal cell carcinoma.
Carcinoma, Renal Cell
/ genetics
Humans
Kidney Neoplasms
/ genetics
Whole Genome Sequencing
Mutation
Von Hippel-Lindau Tumor Suppressor Protein
/ genetics
Prognosis
Male
Female
DNA Copy Number Variations
Middle Aged
Epigenesis, Genetic
Aged
Gene Expression Regulation, Neoplastic
Immunotherapy
/ methods
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
15 Jul 2024
15 Jul 2024
Historique:
received:
28
11
2023
accepted:
17
06
2024
medline:
16
7
2024
pubmed:
16
7
2024
entrez:
15
7
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 39009593
doi: 10.1038/s41467-024-49692-1
pii: 10.1038/s41467-024-49692-1
doi:
Substances chimiques
Von Hippel-Lindau Tumor Suppressor Protein
EC 2.3.2.27
VHL protein, human
EC 6.3.2.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5935Subventions
Organisme : Cancer Research UK (CRUK)
ID : C1298/A8362, A29911, FC10988
Organisme : Wellcome Trust (Wellcome)
ID : 214388, FC10988
Organisme : RCUK | Medical Research Council (MRC)
ID : FC10988
Organisme : DH | National Institute for Health Research (NIHR)
ID : A109
Organisme : Rosetrees Trust
ID : A2204
Organisme : Melanoma Research Alliance (MRA)
ID : 686061
Investigateurs
Mehran Afshar
(M)
Oyeyemi Akala
(O)
Janet Brown
(J)
Guy Faust
(G)
Kate Fife
(K)
Victoria Foy
(V)
Styliani Germanou
(S)
Megan Giles
(M)
Charlotte Grieco
(C)
Simon Grummet
(S)
Ankit Jain
(A)
Anuradha Kanwar
(A)
Andrew Protheroe
(A)
Iwan Raza
(I)
Ahmed Rehan
(A)
Sarah Rudman
(S)
Joseph Santiapillai
(J)
Naveed Sarwar
(N)
Pavetha Seeva
(P)
Amy Strong
(A)
Maria Toki
(M)
Maxine Tran
(M)
Rippie Tutika
(R)
Tom Waddell
(T)
Matthew Wheater
(M)
Informations de copyright
© 2024. The Author(s).
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