NF1 loss is sufficient for plexiform neurofibroma formation, but subsequent CDKN2A/B loss leads to the transitory premalignant stage defined as atypical neurofibromatous neoplasm of uncertain biologic potential (ANNUBP), and further hits disrupting the epigenetic regulator Polycomb Repressive Complex 2 (PRC2) lead to MPNST7–9. The gene discussed is NF1; the disease is neurofibroma.