From a diagnostic standpoint, taken together biallelic NF1 loss and CDKN2A/B define the ANNUBP state, while PRC2 loss (±TP53) with widespread CNVs and other pathway rewiring (RTKs, WNT/HIPPO, and PI3K–mTOR) marks the malignant conversion to MPNST. This evidence concerns the gene NF1 and malignant peripheral nerve sheath tumor.