As for modifiers, inactivation of the TP53/p53 gene, deletion of the CDKN2A/p16 gene, and loss of PTEN are all important in the progression from low-grade neurofibroma (atypical or low-grade malignancy) to MPNST under the effect of biallelic inactivation of NF1 (42, 43, 98). This evidence concerns the gene NF1 and malignant peripheral nerve sheath tumor.