Lack of detectable neoantigen depletion signals in the untreated cancer genome

Nat Genet. 2019 Dec;51(12):1741-1748. doi: 10.1038/s41588-019-0532-6. Epub 2019 Nov 25.


Somatic mutations can result in the formation of neoantigens, immunogenic peptides that are presented on the tumor cell surface by HLA molecules. These mutations are expected to be under negative selection pressure, but the extent of the resulting neoantigen depletion remains unclear. On the basis of HLA affinity predictions, we annotated the human genome for its translatability to HLA binding peptides and screened for reduced single nucleotide substitution rates in large genomic data sets from untreated cancers. Apparent neoantigen depletion signals become negligible when taking into consideration trinucleotide-based mutational signatures, owing to lack of power or to efficient immune evasion mechanisms that are active early during tumor evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Binding Sites
  • Codon
  • Databases, Factual
  • Genome, Human
  • HLA Antigens / metabolism*
  • Humans
  • Mutation Rate
  • Mutation*
  • Neoplasms / genetics*
  • Selection, Genetic
  • T-Lymphocytes, Cytotoxic / immunology


  • Antigens, Neoplasm
  • Codon
  • HLA Antigens