Distribution of cases and mutations according to ROSE clustering subgroups. (A) Distribution of the 8 patient subgroups identified by unsupervised clustering of gene expression profiles using the ROSE method.12 The subgroups, labeled contiguously from R1 to R8, include 2 subgroups associated with known recurrent cytogenetic abnormalities: R1 with translocations of MLL and R2 with TCF3-PBX1 fusion, 1 subgroup that lacks sentinel abnormality (R7), 1 subgroup with good outcome (R6), and 1 subgroup with poor outcome (R8).12 (B) Somatic alteration profiles incorporating both sequence mutations and CNAs in TP53/RB1 signaling, B-cell development, Ras signaling, and JAK signaling pathways. The frequency of patients exhibiting mutations in these 4 pathways among the 8 ROSE gene-expression subgroups differs significantly from the null hypothesis (ie, that the mutations are randomly distributed across all 8 subgroups) with a P value of 9.38 × 10−7, 3.38 × 10−8, 1.53 × 10−7, and 2.16 × 10−10 for TP53/RB1 signaling, B-cell development, Ras signaling, and JAK signaling, respectively by χ2 test.
