Illustration of DNA methylation alterations observed in B-cell malignancies. Several types of tumor-specific changes have been observed in genome-wide DNA methylation studies and are commonly associated with chromatin states in normal B cells. Global hypomethylation is enriched in intergenic regions associated with heterochromatin and quiescent chromatin states. Additional targeted hypomethylation occurs across the methylome of malignant B cells, which is enriched in active gene bodies and the binding sites of overexpressed transcription factors (TFs) and in regions immediately downstream of promoters. Hypermethylation of enhancer regions resulting in enhancer decommissioning is also enriched in gene bodies and correlates with loss of TF expression. Finally, all B-cell malignancies demonstrate hypermethylation of promoters and other sequences associated with polycomb repression in precursory normal cells.