Gene expression changes associated with c-MYC target gene signature are enriched in mouse Eμ-Myc Tfap4+/− tumors and TFAP4-mutated BL patient samples. (A) Volcano plot showing gene expression changes between pretransformed Eμ-Myc Tfap4+/+ and Eμ-Myc Tfap4+/− B220+ IgM− BM cells. Log2-fold change and P values were calculated using a limma R package through the Phantasus application. Red dashed lines indicate cutoff thresholds for fold-change >1.8 and P < .05. The top 5 most DEGs in either direction are labeled. (B) Annotation and z score heat map of genes differentially expressed by >1.8-fold in (A). Genes bound by TFAP4 or cobound by TFAP4 and MYC, as determined by chromatin immunoprecipitation sequencing, are shown in red and blue, respectively. (C) Expression of DEGs, defined in (B), by pretransformed pro/pre-B cells from mice with the indicated Tfap4 genotypes. Upper panel: upregulated genes; lower panel: downregulated genes. (D) GSEA of Tfap4-deficient/mutated vs Tfap4-WT/nonmutated mouse tumor B cells or human BL samples relative to the indicated gene set signatures. Dot sizes, colors, and color gradients indicate the net enrichment score, positive or negative enrichment, and adjusted P value, respectively. (E) GSEA illustrating the selective upregulation of MYC target genes in Tfap4-deficient/haploinsufficient mouse tumors (top panels) and TFAP4-mutated human sporadic (middle panels) or endemic (bottom panels) BL samples. (F) K-means clustering (10 clusters) of genes expressed in pro/pre-B tumor cells from Eμ-Myc mice with indicated Tfap4 genotypes. Het, heterozygous; max, maximum; min, minimum; NES, net enrichment score; Padj, adjusted P value; RPKM, reads per kilobase of transcript, per million mapped reads.