Integrating RNA sequencing data from neurofibroma cells with CRISPR knockout of PRC2 components22 revealed both MPNST and PRC2-mutant neurofibroma cells demonstrated suppression of Schwann cell differentiation markers (S100B, SOX10), enrichment of de-differentiated early neural crest markers (EN1, SOX9, FOXF1), and enrichment of Ras/Raf/MEK/ERK target genes (DUSP6, SPRY2, ETV4) (Supplementary Fig. 5c–e). Here, SPRY2 is linked to plexiform neurofibroma.