Figure 7
From: Molecular subtypes of breast cancer are associated with characteristic DNA methylation patterns
Potential model for the relations between luminal differentiation and breast cancer subtypes. PRC2-mediated gene silencing through trimethylation of H3K27 is common in stem/progenitor cells and would be characterised by high EZH2 expression and PRC2 targets having both low expression and unmethylated CpG sites. These characteristics match our findings for basal-like tumours. PRC2 is then displaced (upper path) and PRC2 targets are preferentially activated to promote differentiation. Such a committed cell state would be characterised by low EZH2 expression and PRC2 targets with both high expression and unmethylated promoters. These characteristics match our findings for lumA tumours. In cancer cells, an alternative route for differentiation (lower path), would be to more stably silence PRC2 target genes by promoter methylation. PRC2 associates with DNA methyltransferases (DNMTs) leading to hypermethylation of PRC2 targets. Such a committed cell state would be characterised by low EZH2 expression and PRC2 targets with both low expression and hypermethylated CpG sites. These characteristics match our findings for lumB tumours.