Fig. 4

Combined BET and CDK2 inhibition targets the MYC transcriptional output in MYC-amplified human medulloblastoma. a–d GSEA result for the oncogenic signature-related gene set (MYC_UP.V1_UP) most strongly downregulated in cerebellar cells (a) and MB002-JQ1+Milciclib-6h (d) as compared to MB002-DMSO-6h; the GSEAs for the same gene set are shown comparing MB002-DMSO-6h with MB002-JQ1-6h (b) and MB002-Milciclib-6h (c). Enrichments were considered significant if FDR < 0.05. e, f Venn diagrams displaying the number of genes significantly upregulated (e) or significantly downregulated (f) in each treatment as compared to DMSO and the overlap of regulated genes between treatments. g Bar plot depicting the number of genes significantly downregulated in two MYC target gene-related gene sets in GTML-JQ1-6h, GTML-Milciclib-6h, or GTML-JQ1+Milciclib-6h; gene sets were identified in a and Supplementary Figure 4a. h, i Venn diagrams showing the number of genes upregulated (h) or downregulated (i) in GTML-DOX-6h, GTML-JQ1+Milciclib-6h, and MB002-JQ1 + Milciclib-6h as compared to GTML-DMSO-6h and the overlap of regulated genes between treatments. Genes were considered significantly regulated if at least one condition was expressed, i.e., log10(FPKM + 1) > 0.50 (GTML) or log10(FPKM + 1) > 0.60 (MB002), the FDR-adjusted p-value q < 0.05, and if log2(FC) > log2(1.5) (upregulated) or log2(FC) < −log2(1.5) (downregulated). j The ten gene sets with top enrichment according to a GSO analysis of the shared 71 downregulated genes from i