Genes mutated by AID in proliferating and resting leukemic cells. (A) Quantification of mutations in Ki67⁺ cells according to occurrence at canonical and noncanonical AID hotspots, and C>T transitions in CpG for TCL1 and DT-AID animals. Analyses of these data show that the c-AID mutation signature was significantly greater in the DT-AID than in the TCL1 mice (median, 121 ± 40 vs 18 ± 9, respectively; P = .027, 2-tailed, unpaired Student t test). (B) Genomic context of AID-related variants in Ki67⁺ cells of TCL1 and DT-AID mice. Significant differences using the 1-tailed exonic, unpaired Student t test (P = .04), ncRNA (P = .04), and 3′UTR (P = .03), were found. *P < .05 (A-B). (C) Graphical representation of the genes affected by nonsynonymous mutations (exonic, UTRs, and up/downstream regions), which adhered to the c-AID context in Ki67⁺ and Ki67⁻ cells. Figure was generated using genes with >5 c-AID mutations; these are highlighted in bold letters. Red bold letters denote gene drivers described in CLL^30,52  and DLBCL⁵³  and in the KI67⁺ fraction. Genes underlined and in bold letters are mutated members of the Wnt-signaling pathway. (D) c-AID mutations were selected and functionally annotated using statistical overrepresentation (KEGG pathways; Fisher exact test). Wnt pathways with the mutated genes affected by c-AID and nonsynonymous mutations are shown. Black asterisks identify genes with c-AID mutations in Ki67⁺ and Ki67⁻ fractions. Red asterisks identify genes with c-AID mutations only present in the Ki67⁺ fraction. As depicted, genes involved in these pathways and previously associated with tumor progression such as Lef-1, Tcf-7, Sox4, Prkch, and Celsr-1 were found.