"MHC-I genotype restricts the landscape of recurrent oncogenic mutations" published in Cell

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.

https://doi.org/10.1016/j.cell.2017.09.050

Hannah Carter
Hannah Carter
Principal Investigator

Dr. Carter is an Associate Professor in the UCSD Department of Medicine, Division of Medical Genetics. She received her Ph.D. in Biomedical Engineering from Johns Hopkins University and her M.Eng. in Electrical and Computer Engineering from the University of Louisville. She is an Azrieli Global Scholar, a Siebel Scholar and a recipient on a 2013 NIH Director’s Early Independence Award.

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