Novel subtype with IDH1/2 mutations. (A) Variant allele frequencies of IDH1/2 and other somatic mutations detected using whole-exome sequencing in 3 representative cases with IDH1/2 mutations. Variants in regions with abnormal copy number or with sequence depth <50 were excluded. IDH1 R132C and IDH2 R140Q mutations are shown in green. (B-D) Significantly enriched gene signatures for IDH1/2-mut ALL (n = 6) from GSEA of RNA sequencing data from 327 cases (323 Ph^– B-ALL plus 4 Ph⁺ ALL) using Reactome gene sets. (E) DNA methylation clusters in 16 cases of B-ALL (supplemental Table 1), including cases of the IDH1/2-mut (n = 3), KMT2A (n = 3), Ph-like (n = 3), TCF3-PBX1 (n = 3), and ZNF384 (n = 4) subtypes with consensus unsupervised clustering with top 0.1% most variable methylation probes (n = 866) using Ward’s method. Information regarding disease subtypes is shown at the top of the panel. A case with IGH-CRLF2 (B213-069), which was not included in RNA-seq analysis, was assigned to the Ph-like group. (F) Differentially methylated regions in 3 IDH1/2-mut ALL cases compared with 13 other B-ALL cases. Statistically significant (q < 0.1) hyper (red) and hypo (blue) methylated probes, and the level of methylation are expressed by β value.