A pan-cancer analysis of PBAF complex mutations and their association with immunotherapy response.
Adult
Aged
Aged, 80 and over
Carcinoma, Renal Cell
/ genetics
Chromosomal Proteins, Non-Histone
/ genetics
Cohort Studies
DNA-Binding Proteins
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Immunotherapy
/ methods
Kaplan-Meier Estimate
Kidney Neoplasms
/ genetics
Middle Aged
Mutation
Transcription Factors
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 08 2020
20 08 2020
Historique:
received:
19
12
2019
accepted:
23
07
2020
entrez:
22
8
2020
pubmed:
21
8
2020
medline:
15
9
2020
Statut:
epublish
Résumé
There is conflicting data regarding the role of PBAF complex mutations and response to immune checkpoint blockade (ICB) therapy in clear cell renal cell carcinoma (ccRCC) and other solid tumors. We assess the prevalence of PBAF complex mutations from two large cohorts including the pan-cancer TCGA project (n = 10,359) and the MSK-IMPACT pan-cancer immunotherapy cohort (n = 3700). Across both cohorts, PBAF complex mutations, predominantly PBRM1 mutations, are most common in ccRCC. In multivariate models of ccRCC patients treated with ICB (n = 189), loss-of-function (LOF) mutations in PBRM1 are not associated with overall survival (OS) (HR = 1.24, p = 0.47) or time to treatment failure (HR = 0.85, p = 0.44). In a series of 11 solid tumors (n = 2936), LOF mutations are not associated with improved OS in a stratified multivariate model (HR = 0.9, p = 0.7). In a current series of solid tumors treated with ICB, we are unable to demonstrate favorable response to ICB in patients with PBAF complex mutations.
Identifiants
pubmed: 32820162
doi: 10.1038/s41467-020-17965-0
pii: 10.1038/s41467-020-17965-0
pmc: PMC7441387
doi:
Substances chimiques
Chromosomal Proteins, Non-Histone
0
DNA-Binding Proteins
0
PBRM1 protein, human
0
SWI-SNF-B chromatin-remodeling complex
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4168Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA232097
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA082088
Pays : United States
Commentaires et corrections
Type : CommentIn
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