In our opinion, this might be explained by the fact that the methylation of histones represents the final stretch of epigenetic modification being influenced by much more players than EZH2. This hypothesis is supported by data from epithelial tumors: in a large cohort of breast cancers, although subtype-dependent overexpression of EZH2 and H3K27m3 overexpression were found, not a single EZH2 mutation could be detected [17]. This evidence concerns the gene EZH2 and breast carcinoma.