Escape from nonsense-mediated decay associates with anti-tumor immunogenicity.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
30 07 2020
30 07 2020
Historique:
received:
30
07
2018
accepted:
30
06
2020
entrez:
1
8
2020
pubmed:
1
8
2020
medline:
9
9
2020
Statut:
epublish
Résumé
Frameshift insertion/deletions (fs-indels) are an infrequent but highly immunogenic mutation subtype. Although fs-indels are degraded through the nonsense-mediated decay (NMD) pathway, we hypothesise that some fs-indels escape degradation and elicit anti-tumor immune responses. Using allele-specific expression analysis, expressed fs-indels are enriched in genomic positions predicted to escape NMD, and associated with higher protein expression, consistent with degradation escape (NMD-escape). Across four independent melanoma cohorts, NMD-escape mutations are significantly associated with clinical-benefit to checkpoint inhibitor (CPI) therapy (P
Identifiants
pubmed: 32733040
doi: 10.1038/s41467-020-17526-5
pii: 10.1038/s41467-020-17526-5
pmc: PMC7393139
doi:
Substances chimiques
Antigens, Neoplasm
0
Biomarkers, Tumor
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
3800Subventions
Organisme : Wellcome Trust
ID : FC001169
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001169
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001169
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Cancer Research UK
ID : C50947/A18176
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P014712/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C69256/A30194
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
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