Extended Data Fig. 2: Characterization of tumor-specific DNA methylation signatures.

a, First 9 components of a Principal Component Analysis for normal and neoplastic B cells. Samples sizes are the same as in Fig. 1a. The same sample size applies also for panel b, c and d. b, Percentages of de novo DNA methylation signatures over the total DNA methylome. All de novo hyper- and hypomethylation from the five B-cell tumors analyzed are considered together to derive each respective percentage. c, Heatmap showing B-cell tumor-specific hypermethylation and the number of CpGs located at active regulatory regions (marked by H3K27ac). To calculate CpG enrichments in regulatory regions, the number of CpGs falling in regulatory regions were compared with the same number of de novo CpGs 10,000 times randomly chosen from the DNA methylome fraction with potential tumor-specific signatures falling in regulatory regions. d, Distribution of mean methylation levels of CpGs from de novo B-cell tumor-specific DNA methylation signatures across all normal and neoplastic B cell samples subtypes. The number of samples used to calculate the means is shown in Fig. 1a and the number of CpGs analyzed are those from Fig. 2b. e, Genomic distribution for de novo DNA methylation changes in B-cell tumors. Barplots represent single data values. f, Gene expression percentile of TFs showing the most significant p-values and frequencies for TFs binding site predictions (Methods) in de novo hypomethylation signatures in each B-cell tumor from Fig. 2d. Sample sizes for gene expression analyses in tumor samples are the same than in Fig. 4e. Center line, box limits, whiskers and points represent the median, 25th and 75th percentiles, 1.5x interquartile range and individual samples, respectively.