(a) PRC2 consists of four core components: EED, EZH2, SUZ12 and RBBP4/7 (158). There are also several PRC2 accessory polypeptides, not be discussed here. PRC2 trimethylates lysine 27 of histone H3 (158). EED (embryonic ectoderm development) recognizes trimethylated histone H3 lysine 27 (H3K27me3), allosterically activating the enzymatic activity of the entire complex (159,160). EZH2 is the catalytic component of PRC2, trimethylating H3K27 via its SET domain (158). SUZ12 is necessary for the catalytic activity of PRC2 and may regulate PRC2 activity through interactions with noncoding RNAs (161,162). RBBP4/7 recognizes unmodified histone H3, while active chromatin marks like H3K4me3 and H3K36me3 allosterically inhibit PRC2 activity (163). Loss of function mutation frequencies of PRC2 components in MPNST are denoted in red. (b) Publicly available data on PRC2 mutations in MPNSTs (cbioportal.org). Mutations in SUZ12 and EED occurred in 11 of 15 samples. Mutations in these two PRC2 core components are mutually exclusive (p = 0.042).