MHC-I Genotype-Based Scores Predict Individual Oncogenic Mutations

NEW YORK (GenomeWeb) – A team of investigators led by researchers at the University of California, San Diego has developed a way to predict individuals’ cancer susceptibilities from knowledge of their MHC-I genotypes.

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 that each individual carries defines the sub-peptidome that can be effectively presented, the researchers wrote yesterday in Cell.

They hypothesized that oncogenic mutations could arise in gaps in personal MHC-I presentation. They developed a residue-centric patient presentation score for 9,176 cancer patients across 1,018 recurrent oncogenic mutations, and found that the patients’ personal MHC-I genotype-based scores could predict their oncogenic mutational landscapes.

“Accordingly, poor presentation of a mutation across patients was correlated with higher frequency among tumors,” the authors wrote. “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.”

The researchers began by characterizing the interactions between patient MHC-I allele combinations and recurrent cancer mutations for thousands of tumors from The Cancer Genome Atlas, and

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