DNA methylation- and PRC-silenced genes in BC predict poor outcome in patients with CP. Table summarizing preranked GSEA results for MBC vs CP (A). Normalized enrichment score (NES), FDR, as well as the identity of the genes that drive the enrichment are provided (for details, see “Methods”; supplemental Tables 39-41). A negative NES value denotes that genes downregulated from CP to BC in our samples are enriched for the indicated data sets. (B) Top GO terms, with FDR scores, for genes in panel A. (C) CP to BC progression model that illustrates that, despite genetic heterogeneity, there is a convergence in progression-specific transcriptomes and methylomes that are driven by BMI1 and EZH2. Specifically, EZH2 directs BC-specific DNA hypermethylation that inhibits cell differentiation and tumor suppressor programs, whereas BMI1 also inhibits cell death.