Evolutionary dynamics of neoantigens in growing tumors.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
08
01
2019
accepted:
06
07
2020
pubmed:
16
9
2020
medline:
25
11
2020
entrez:
15
9
2020
Statut:
ppublish
Résumé
Cancers accumulate mutations that lead to neoantigens, novel peptides that elicit an immune response, and consequently undergo evolutionary selection. Here we establish how negative selection shapes the clonality of neoantigens in a growing cancer by constructing a mathematical model of neoantigen evolution. The model predicts that, without immune escape, tumor neoantigens are either clonal or at low frequency; hypermutated tumors can only establish after the evolution of immune escape. Moreover, the site frequency spectrum of somatic variants under negative selection appears more neutral as the strength of negative selection increases, which is consistent with classical neutral theory. These predictions are corroborated by the analysis of neoantigen frequencies and immune escape in exome and RNA sequencing data from 879 colon, stomach and endometrial cancers.
Identifiants
pubmed: 32929288
doi: 10.1038/s41588-020-0687-1
pii: 10.1038/s41588-020-0687-1
pmc: PMC7610467
mid: EMS118013
doi:
Substances chimiques
Antigens, Neoplasm
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
1057-1066Subventions
Organisme : Wellcome Trust
ID : 105104/Z/14/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202778/B/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202778/Z/16/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203141/7/16/7
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 202778
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 108861/7/15/7
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U54 CA143970
Pays : United States
Organisme : Cancer Research UK
ID : A22909
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 097319/Z/11/Z
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U54 CA217376
Pays : United States
Organisme : Wellcome Trust
ID : 097319
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A19771
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 203141
Pays : United Kingdom
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