Five dominant amino acid substitution signatures shape tumour immunity

ABSTRACT: Although numerous mutational processes operate in cancer, their functional impacts are unclear. We hypothesized that certain mutation sources preferentially generate amino-acid substitutions that evade immune recognition, producing immune-cold tumours regardless of tissue or mutation load. By analysing 9300 cancer exomes and performing mutagenesis experiments, we mapped links between mutagens, DNA-repair defects, and amino-acid substitution signatures (AAS). Surprisingly, the spectrum collapsed into five recurrent AAS with distinct functional profiles. AAS4-generated by alkylating agents and mismatch-repair (MMR) deficiency and enriched in kidney and liver cancers-is less likely to accumulate hydrophobic residues, yielding poorly immunogenic neopeptides. These tumours display immune-deser

SUBMITTER: Szilvia Juhasz 

PROVIDER: S-SCDT-10_1038-S44320-026-00193-X | biostudies-other |

REPOSITORIES: biostudies-other