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Lack of detectable neoantigen depletion signals in the untreated cancer genome.

Journal article
Authors Jimmy Van den Eynden
Alejandro Jiménez-Sánchez
Martin L Miller
Erik Larsson
Published in Nature genetics
Volume 51
Issue 12
Pages 1741-1748
ISSN 1546-1718
Publication year 2019
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 1741-1748
Language en
Links dx.doi.org/10.1038/s41588-019-0532-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Medical Genetics, Cancer and Oncology, Genetics, Bioinformatics and Systems Biology

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.

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