MHC-I Genotype Restricts the Oncogenic Mutational Landscape.
Cell
; 171(6): 1272-1283.e15, 2017 Nov 30.
Article
en En
| MEDLINE
| ID: mdl-29107334
ABSTRACT
MHC-I molecules expose the intracellular protein content on the cell surface, allowing T cells to detect foreign or mutated peptides. The combination of six MHC-I alleles each individual carries defines the sub-peptidome that can be effectively presented. We applied this concept to human cancer, hypothesizing that oncogenic mutations could arise in gaps in personal MHC-I presentation. To validate this hypothesis, we developed and applied a residue-centric patient presentation score to 9,176 cancer patients across 1,018 recurrent oncogenic mutations. We found that patient MHC-I genotype-based scores could predict which mutations were more likely to emerge in their tumor. Accordingly, poor presentation of a mutation across patients was correlated with higher frequency among tumors. These results support that MHC-I genotype-restricted immunoediting during tumor formation shapes the landscape of oncogenic mutations observed in clinically diagnosed tumors and paves the way for predicting personal cancer susceptibilities from knowledge of MHC-I genotype.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Antígenos de Histocompatibilidad Clase I
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Presentación de Antígeno
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Mutación
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Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Cell
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos