No Evidence that MHC Genotype Affects Oncogenic Mutation Landscapes

Abstract

MHC molecules are capable of presenting neoantigens resulting from somatic mutations on cell surfaces, potentially directing immune responses against cancer. This led to the hypothesis that cancer driver mutations may occur in gaps in the capacity to present neoantigens that are dependent on MHC genotype. If this is correct, it may help to predict the driver mutations that are likely to be observed in an individual from genotype data. Two papers supporting this hypothesis were published in Cell, reporting that driver mutations that occur frequently tend to be poorly presented by common MHC alleles and proposing that MHC genotype is predictive of the driver mutations observed in a patient. Here we demonstrate that these results are a consequence of unjustified statistical assumptions and that the data on which they are based do not provide any evidence of an effect of MHC genotype on the oncogenic mutation landscape.