To examine the role of PRC2 loss in MPNST while minimizing cell line–specific confounding factors, we generated and validated PRC2-isogenic human MPNST cells using CRISPR/Cas9-mediated knockout of the PRC2 core component SUZ12 in a PRC2-wt, NF1–/– CDKN2A–/– M3 cell line derived from a human NF1–associated MPNST (Figure 3A). Here, SUZ12 is linked to malignant peripheral nerve sheath tumor.