Relapse-enriched somatic variants in pediatric ALL. (A) ALL subtypes of the patient cohort. The number of cases in each subtype and in B- or T-lineage is labeled in the outer and the inner circles, respectively. Subtypes of singleton cases are binned to B/Other (IGH-MYC and hypodiploid) or T/Other (HOXA). D, diagnosis; R, relapse. (B) Schematic showing sequencing performed and number of patients (n) sequenced with each platform. (C) Pathways mutated among shared variants (diagnosis and relapse [D+R]) compared with relapse-specific variants (R); pathways are defined in supplemental Table 5. Color indicates mutation type identified in a single patient; box indicates pathways enriched at relapse. Slice width represents the proportion of patients with mutation of at least 1 gene in indicated pathway. (D) Heatmap of significantly mutated genes and known driver genes across the cohort, with genes in rows and patients in columns. The 12 genes at top are those enriched specifically among relapse-specific variants (supplemental Methods), and genes in the bottom portion are frequently present at both diagnosis and relapse. At right, a bar plot of the percentage of patients mutated for each gene is shown, along with the pathway to which the gene belongs. Gray indicates that the mutation is shared at diagnosis and relapse (D+R), red indicates relapse-specific (R), and blue indicates diagnosis-specific (D). Subtypes and B- vs T-lineage are indicated at top. CDKN2A mutations occurred in 49% of samples, which is above the axis limit.