Extended Data Fig. 5: Mutations are enriched at intragenic SEs encompassing H3K4me3⁺ promoters.

a. Overall mutation frequency (left panel) and percentage of hypermutated E/SEs (right panel; see Methods and Fig. 1b for definition) in 29 DLBCL cell lines. Data are provided separately for E/SEs encompassing promoters (i.e. overlapping with H3K4me3⁺) and devoid of promoters (i.e. not overlapping with H3K4me3⁺ regions and TSS-distal). Each dot represents one cell line, and mutation frequencies are expressed as fold changes vs. the background mutation frequency of the same cell line, set as 1 (dotted line). A horizontal red bar defines the mean across all 29 cell lines.b. Overall mutation frequency (left panel) and percentage of hypermutated active promoters (H3K27Ac⁺ H3K4me3⁺ regions) in 29 DLBCL cell lines. Data are provided separately for promoters embedded in SEs, promoters embedded in Es, and classical active promoters not embedded in E/SEs. Each dot represents one cell line, and the mutation frequencies are expressed as fold changes vs. the background mutation frequency of the same cell line, set as 1 (dotted line). A horizontal red bar defines the mean across all 29 cell lines. c. Overall mutation frequency (left panel) and percentage of hypermutated core E/SEs (right panel; see Methods and Fig. 1d for definition) in 93 primary DLBCL biopsies. Data are provided separately for E/SEs encompassing promoters and E/SEs devoid of promoters (defined as in a). Each dot represents one sample, and mutation frequencies are expressed as fold changes vs. the background mutation frequency of the same sample, set as 1 (dotted line). A horizontal red bar defines the mean across all 93 DLBCL samples. Note that these frequencies represent an underestimate of the actual mutation frequencies as, in the absence of sample-specific H3K27Ac data, the region interrogated represents the union of the core E/SEs found in all 29 cell lines. d. Overall mutation frequency (left panel) and percentage of hypermutated active promoters (H3K27Ac⁺ H3K4me3⁺ regions) in 93 cases of primary DLBCL. Data are provided separately for promoters embedded in SEs, promoters embedded in Es, and classical active promoters not embedded in E/SEs. Each dot represents one DLBCL biopsy, and mutation frequencies are expressed as fold changes vs. the background mutation frequency of the same sample, set as 1 (dotted line). A horizontal red bar defines the mean across all 93 DLBCL biopsies. All p-values were calculated by two-sided Wilcoxon rank-sum test after BH correction.

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