Lack of detectable neoantigen depletion signals in the untreated cancer genome Journal Article
| Authors: | Van den Eynden, J.; Jiménez-Sánchez, A.; Miller, M. L.; Larsson, E. |
| Article Title: | Lack of detectable neoantigen depletion signals in the untreated cancer genome |
| Abstract: | 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. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | unclassified drug; somatic mutation; binding affinity; amino acid substitution; genotype; mutational analysis; cancer genetics; t lymphocyte receptor; cytotoxic t lymphocyte; protein structure; antigen binding; hla a antigen; hla b antigen; hla c antigen; signal detection; antigen presenting cell; hla antigen; major histocompatibility antigen class 1; hydrophobicity; purifying selection; immunological parameters; trinucleotide; human; article; nonapeptide; neoantigen; hla binding mutation ratio; neoantigen depletion signal |
| Journal Title: | Nature Genetics |
| Volume: | 51 |
| Issue: | 12 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2019-12-01 |
| Start Page: | 1741 |
| End Page: | 1748 |
| Language: | English |
| DOI: | 10.1038/s41588-019-0532-6 |
| PUBMED: | 31768072 |
| PROVIDER: | scopus |
| PMCID: | PMC6887557 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 January 2020 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work