Extended Data Fig. 1: Analyses related to sample selection and annotation of stably-methylated CpGs.

a, Principal component analysis and hierarchical clustering of synchronic unpurified/purified DNA methylation profiles obtained with EPIC array from MCL and CLL patients. Colors represent the same sample, with FCM-based purities highlighted in each sample. MCL, mantle cell lymphoma. CLL, chronic lymphocytic leukemia. b, Correlations and Passing Bablock regression fits of gold-standard methods for tumor purity prediction (FCM and genetic-based) against DNA methylation-based tumor purity prediction for MCL and CLL patients in initial and validation series. Samples sizes are: MCL initial series, n=32; MCL validation series, n=56; CLL cohort 1, n=109 and CLL cohort 2, n=178 patients. Shaded area represents 95% confidence intervals. Pearson correlation and derived p-values are also shown. c, Pearson correlations and Passing Bablock regression fits for gold-standard methods for tumor purity predictions (FCM and genetic-based) against DNA methylation-based tumor purity predictions in MM and DLBCL patients. Sample sizes are: MM, n=100 and DLBCL, n=55 patients and are the same as in panel d. Shaded area represents 95% confidence intervals. Pearson correlation and derived p-values are also shown. d, Pan-B cell DNA methylation signature used to deconvolute DNA methylation data and obtain B-cell tumor purities in B-cell tumors. The DNA methylation levels for the Pan-B-cell DNA methylation signature is shown for microenvironmental cells as well as MM and DLBCL. Bar plots representing DNA-methylation based predictions as well as gold standard-based predictions for MM and DLBCL are represented on the top of the heatmaps. e, Chromatin state genome segmentation with the CHMM software using the 6 histone marks used in the whole study for normal B cells, MCL, CLL and MM primary cases as well as for KARPAS-422 and SUDHL-5 DLBCL cells lines. f, Genomic distribution of stably methylated and unmethylated CpGs in normal and neoplastic B cell. Barplots represent single data values. g, Example gene showing stably unmethylated CpGs at promoters and stably methylated CpGs at gene body in normal and neoplastic B cells. A total of 98 CpGs are shown. h, Gene ontology analysis of genes showing both stably methylated and stably unmethylated CpGs in normal and neoplastic B cells.