Figure 4
Methylation changes at progression-associated CpGs show similarities to memory B cells. (a) Methylation levels for CLL samples at progression-associated CpGs, grouped with naive B cells (CD5+ and normal) and memory B cells (IgA+IgG+ and IgM+IgD+). IGHV mutation status of CLL samples is shown along the top according to the legend colors. (b) Schematic representation showing the number of CpG sites that differ by at least 10% between the average of the six memory B-cells, the six naive B cells, and the 27 CLL samples taken at the first time point. The number of CpGs that also change during progression are reported under the number and as a percent of the sites that differ. (c) Barplot showing the enrichment of progression-associated CpGs near H3K27me3 marks and all progression-associated CpGs compared with all CpGs that differ at least 10% between comparisons of the three cell types. P-values were calculated using the hypergeometric test based on the counts in each category. (d) Venn diagram showing the overlap of progression-associated sites that were near H3K27me3 regions and also differed at least 10% between comparisons of cell types shown in 4B. (e). Barplots showing the percent of CpGs that change methylation status in the same direction (both increase or both decrease) during progression (CLLDX to CLLTX) as between comparisons of the cell-types in 4B. (f). Heatmap showing methylation Beta levels from the ICGC data at progression-associated CpGs. Methylation levels are shown as the difference between the sample and the average of six naive B-cell samples. Black and grey lines indicate which rows are near H3K27me3 regions (black) or not (grey).
