Fig. 4: EZH2-mutant follicular lymphomas systematically display altered H3K27me3 profiles.

a Workflow of cohort sample selection and molecular analysis. (*For tumors analyzed at multiple time points, DRAGON analysis was performed at all time points.) b Disease event timeline indicating timing of biopsy collection and types of analysis conducted. c Volcano plot comparing gene expression between EZH2-WT and EZH2-mutant lymphoma samples and highlighting differentially expressed genes in red (up-regulated) and blue (down-regulated). FC, fold change. d Gene ontology biological process (GOBP) gene sets enriched (FDR < 0.25) among genes identified as differentially expressed between EZH2-WT and -mutant lymphomas were further analyzed by gene set enrichment analysis (GSEA) to compare their normalized enrichment scores (NES) among genes differentially expressed in both our cohort and the Primary RItuximab and MAintenance (PRIMA) cohort⁵⁸. e H3K27me3 ChIP-seq tracks for merged EZH2-WT (n = 4, each in duplicate) and merged EZH2-mutant lymphoma samples (n = 8, each in duplicate) with corresponding genomic annotations shown below. f Violin and box plots showing mean normalized H3K27me3 ChIP-seq read counts for EZH2-WT and -mutant lymphoma samples within all bins of 10 kb across the genome (n = 283,797) (left) or within regions identified as enriched in H3K27me3 (n = 18,784) (right). Boxes represent median and first and third quartiles, while whiskers show minimum and maximum. p-values represent the result of unpaired two-sided t-tests. g Principal component analysis (PCA) of variance among H3K27me3 ChIP-seq experiments performed in duplicate on EZH2-WT and EZH2-mutant lymphoma samples, considering only the 5000 most variable H3K27me3-enriched regions.