Figure 3.
The BC methylome is enriched for PRC targets and regulates differentiation. (A) DNA methylation heat map of NBM (n = 7), CP (n = 28), MBC (n = 18), and LBC (n = 12) β values. Mutational profiles of the commonest recurring gene mutations are depicted for each methylome. *Biphenotypic BC sample with myeloid and lymphoid immunophenotype (“Methods”). (B) Starburst plot depicting the relationship between gene expression and DNA methylation (adjusted P < .05 for both). Numbers indicate probes with number of genes in parentheses. Percentages indicate proportion of probes out of the total. The number of samples used are 28 for CP and 18 for MBC. Pie charts show relative proportions of MSigDB v6.1 gene set functions enriched in each quadrant for gene expression and DNA methylation, whereas pie chart size indicate the relative number of gene sets (not to scale). (C) Genes that are hypermethylated at BC significantly overlapped with genes that are bound by PRC from 2 published data sets.35,36 (D) Heat map showing gene expression changes for DAC compared with dimethyl sulfoxide treatments (adjusted P value < .05 and gene expression Log2 fold-change >0.58 or <−0.58) in 3 primary BC patient samples. (E) Preranked GSEA analysis of the expression profile of DAC-treated primary BC cells that is depleted for HSC and LSC signature but enriched for myeloid differentiation genes.