Fig. 2

Common insertion site and somatic mutation analysis of BCP-ALL cases in Etv6-RUNX1, T2Onc, Pax5 mice. a Transposon common insertion sites (CIS) in B-ALL cases. All CIS shown have a genome-wide p value of <0.025. Alterations in expression levels were determined using RNA-seq data (from 20 ER, Onc, Pax mice that developed B220+, CD19+ BCP-ALL and 8 age-matched ‘control’ ER, Onc, Pax mice that never developed disease), whereby the expression level of a gene in BCP-ALL cases containing insertions in a particular CIS was compared to the expression level of that gene in ‘control’ cases. FC, log fold change; FDR, false discovery rate (significance was assessed at an FDR of 5 %). b Acquired somatic events in B-ALL cases in ER, Onc, Pax mice. Each column represents a sample (individual mouse). Red indicates a stop mutation, brown indicates a splice acceptor variant, yellow indicates a splice region variant (intron) and blue indicates a missense variant. c The fraction of reads (expressed as a percentage) reporting the somatic variant alleles shown in b (in the same order as shown in b). d Schematic diagram of the protein structure of Jak1 and Jak3, showing the locations of the mutations identified in this study. FERM, band 4.1 ezrin; SH2, src-homology domain. e Somatically acquired mutations in Jak1/3 found in ER, Onc, Pax B-ALL tumors in which the corresponding JAK1/3 mutations have been found in human cancers. AA, amino acid. ^*These mutations have been shown to have gain-of-function and/or transforming activity. ^**These cases were pediatric high-risk B-cell progenitor ALL excluding BCR-ABL1+ ALL and hypodiploid ALL. ^***Acute megakaryoblastic leukemia of Down syndrome. ^****An AML with t(15;17)(q22;q12)