Unknown

Dataset Information

0

MHC-I Genotype Restricts the Oncogenic Mutational Landscape.


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.

SUBMITTER: Marty R 

PROVIDER: S-EPMC5711564 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 canc  ...[more]

Similar Datasets

| S-EPMC7236948 | biostudies-literature
| S-EPMC5156680 | biostudies-literature
| S-EPMC7455744 | biostudies-literature
| S-EPMC3918763 | biostudies-literature
| S-EPMC10468661 | biostudies-literature
| S-EPMC3447382 | biostudies-other
| S-EPMC5515252 | biostudies-literature
| S-EPMC9322060 | biostudies-literature
| S-EPMC3708595 | biostudies-literature
| S-EPMC8053980 | biostudies-literature