These studies suggest that in NF1-associated MPNST (vs. sporadic or radiation-induced), development of the fully malignant state commonly involves the following steps: (1) tumor initiation following somatic loss of the second NF1 allele; (2) loss of CDKN2A/B resulting in premalignant ANF/ANNUBP; and (3) loss of PRC2 function initiating malignancy. This evidence concerns the gene CDKN2A and neoplasm.