CDK4 and primitive neuroectodermal tumor: Members of the CDKN2A-CDK4/6-RB1 pathway, including CDKN2A, P14ARF, and RB1 have shown promoter hypermethylation in PNET samples [52,98,99,100], suggesting that the DNA methylation-mediated downregulation of CDKN2A-RB1 signaling might contribute to PNET development.