biostudies-literatureHernandez-Verdin IInstitut National Du CancerAgence Nationale de la RechercheBicocca 2020 Starting Grant and by a Premio Giovani Talenti dell'Università degli Studi di Milano-BicoccaARTC foundationAgence Nationale de la Recherche (French National Research Agency)Institut National Du Cancer (French National Cancer Institute)89https://www.ebi.ac.uk/biostudies/studies/S-EPMC9715662biostudies-literatureUnknown6(1)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) treatNPJ precision oncologyPan-cancer landscape of AID-related mutations, composite mutations, and their potential role in the ICI response.PMC9715662ANR-10-IAIHU-06SIRIC CURAMUSSiRIC CURAMUSAlentorn ASanson MMokhtari KTouat MAkdemir KCDuval ARamazzotti DPeyre MIdbaih AHernandez-Verdin IBielle FCaravagna GLabreche KHoang-Xuan KfalsePan-cancer landscape of AID-related mutations, composite mutations, and their potential role in the ICI response.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) treat2022-01-01T00:00:00Z2022 Dec2026-05-10T06:35:53.733Z2025-04-04T10:58:30.379ZS-EPMC97156623645668510.1038/s41698-022-00331-2