Tumor genomic alterations in severe-combined immunodeficiency bare-lymphocyte syndrome genes are associated with high mutational burden and disproportional neo-antigen rates.

ABSTRACT: The progression of cancer requires mutational adaptation to permit unrestrained proliferation. A fraction of cancer mutations are oncogenic drivers, while others are putative 'passengers' that do not contribute to oncogenesis. However, altered peptides arising from passenger mutations may bind MHCs and activate non-self immunologic signals (i.e. neoantigens), thus requiring immunoediting for cancer persistence. Disruption of antigen processing machinery in tumor cells may diminish this requirement. Here, we show that rare mutations in antigen processing machinery are associated with high mutational burden and increased predicted neoantigen load, providing insights into the mechanisms of high mutation burden in some patients.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6503546 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature