Somatic mutations in Npm1^cA/+, Npm1^cA/+;Nras^G12D/+, and Npm1^cA;Flt3^ITDAMLs. (A) Exome sequencing identifies an increased number of SNVs and small indels in Npm1^cA/+, in comparison with Npm1^cA/+;Nras^G12D/+ (RN-AML) and Npm1^cA;Flt3^ITD (FN-AML) AML samples. Npm1^cA/+ 6.8 ± 0.9, Npm1^cA/+;Nras^G12D/+ 3.3 ± 0.5, and Npm1^cA/+;Flt3^ITD/+ 2.6 ± 0.7 (mean ± SEM) (**P < .01 vs Npm1^cA/+, 1-way analysis of variance, Bonferroni adjusted). Total AMLs sequenced; Npm1^cA/+ (n = 12), Npm1^cA/+;Nras^G12D/+ (n = 14) and Npm1^cA;Flt3^ITD (n = 7). (B) Summary of SNVs/indels detected in AMLs from each genotype, as indicated. Genes mutated in the TCGA AML dataset¹  are depicted in red (exact mutation reported) or in blue (different mutations reported). (C) Co-occurrence of SNVs and copy number variants (CNVs) that have been formally detected in the TCGA AML dataset¹  or identified as common insertion sites in our previously published Npm1^cA/+ Sleeping Beauty Transposon screen.⁷  Mutant allele copy gains, chromosome gains, and losses are depicted separately. For copy number variation, color-coded boxes are based on log2 ratios (aCGH) and are not representative of CNV size. For a complete overview of all CNV and SNV co-occurrences, see supplemental Figure 6.