Quantifying immune-based counterselection of somatic mutations

Somatic mutations in protein-coding regions can generate 'neoantigens' causing developing cancers to be eliminated by the immune system. Quantitative estimates of the strength of this counterselection phenomenon have been lacking. We quantified the extent to which somatic mutations are dep...

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Bibliographic Details
Published in:PLoS genetics 2019-07, Vol.15 (7), p.e1008227-e1008227
Main Authors: Yang, Fan, Kim, Dae-Kyum, Nakagawa, Hidewaki, Hayashi, Shuto, Imoto, Seiya, Stein, Lincoln, Roth, Frederick P
Format: Article
Language:English
Subjects:
Alleles
Antibody diversity
Antigen Presentation
Antigens
Antigens, Neoplasm - genetics
Biology and Life Sciences
Cancer
Cancer prevention
Epigenetics
Gene expression
Genetic aspects
Genetic code
Genetics
Genomes
Genomics
Histocompatibility Antigens Class I - metabolism
Humans
Immune system
Immunologic research
Immunology
Major histocompatibility complex
Medical research
Medicine and Health Sciences
Methods
Mutation
Mutation, Missense
Neoantigens
Patients
Peptides
Peptides - genetics
Proteins
Quantitative research
Research and Analysis Methods
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Summary:Somatic mutations in protein-coding regions can generate 'neoantigens' causing developing cancers to be eliminated by the immune system. Quantitative estimates of the strength of this counterselection phenomenon have been lacking. We quantified the extent to which somatic mutations are depleted in peptides that are predicted to be displayed by major histocompatibility complex (MHC) class I proteins. The extent of this depletion depended on expression level of the neoantigenic gene, and on whether the patient had one or two MHC-encoding alleles that can display the peptide, suggesting MHC-encoding alleles are incompletely dominant. This study provides an initial quantitative understanding of counter-selection of identifiable subclasses of neoantigenic somatic variation.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1008227