CREBBP loss-of-function results in gene expression repression signature. CREBBP loss-of-function results in gene expression repression signature. A–D,

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CREBBP loss-of-function results in gene expression repression signature. CREBBP loss-of-function results in gene expression repression signature. A–D, Supervised analysis of the top 500 most differentially expression genes between CREBBP WT (CREBBPWT) and mutant (CREBBPMUT) follicular lymphoma (FL; A and B), DLBCL patients (C), or between scramble and CREBBP knockdown MD901 cells (D). Columns represent individual samples, rows correspond to the genes. Heat map represents the z-scores of the expression value (RPKM) characterized by RNA-seq. The column on the right represents the proportion of the genes that were repressed (green) or upregulated (red) in CREBBPMUT patient samples as compared with CREBBPWT patient samples (A–C), or in CREBBP knockdown cells as compared with scramble control samples of the respective cohorts (D). Statistical significance was determined by Fisher exact test. E, Summary of the GSEA of the downregulated genes in the top 500 most differentially expressed genes of respective cohorts as compared with ranked gene expression changes between either murine VavP-Bcl2/CrebbpKD and VavP-Bcl2/EV murine tumors (purple bars) or between CREBBP KD and Scr MD901 cells (orange bars). *, significant enrichment (FDR q < 0.05). F, Pathway analysis of the downregulated genes within the top 500 most differentially expressed genes of respective cohorts. Heat map represents the −log10 BH-adjusted P value of each gene set tested. Yanwen Jiang et al. Cancer Discov 2017;7:38-53 ©2017 by American Association for Cancer Research