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Article Dans Une Revue npj Precision Oncology Année : 2022

Pan-cancer landscape of AID-related mutations, composite mutations, and their potential role in the ICI response

Résumé

Abstract Activation-induced cytidine deaminase, AICDA or AID, is a driver of somatic hypermutation and class-switch recombination in immunoglobulins. In addition, this deaminase belonging to the APOBEC family may have off-target effects genome-wide, but its effects at pan-cancer level are not well elucidated. Here, we used different pan-cancer datasets, totaling more than 50,000 samples analyzed by whole-genome, whole-exome, or targeted sequencing. AID mutations are present at pan-cancer level with higher frequency in hematological cancers and higher presence at transcriptionally active TAD domains. AID synergizes initial hotspot mutations by a second composite mutation. AID mutational load was found to be independently associated with a favorable outcome in immune-checkpoint inhibitors (ICI) treated patients across cancers after analyzing 2000 samples. Finally, we found that AID-related neoepitopes, resulting from mutations at more frequent hotspots if compared to other mutational signatures, enhance CXCL13 / CCR5 expression, immunogenicity, and T-cell exhaustion, which may increase ICI sensitivity.

Dates et versions

hal-03885511 , version 1 (05-12-2022)

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Citer

Isaias Hernández-Verdin, Kadir Akdemir, Daniele Ramazzotti, Giulio Caravagna, Karim Labreche, et al.. Pan-cancer landscape of AID-related mutations, composite mutations, and their potential role in the ICI response. npj Precision Oncology, 2022, 6 (1), pp.89. ⟨10.1038/s41698-022-00331-2⟩. ⟨hal-03885511⟩
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