<prompt> Mutation seen in malignant melanoma isN-MYCRB geneCDKN2Ap53  <response>: CDKN2A is a complex locus that encodes three different tumor sup- pressors, p15INK4b, p16INK4a, and p14ARF. Of these, loss of p16INK4a is clearly implicated in human melanoma, and experimental evidence also suppos a role for loss of p14ARF. As already mentioned, p16 INK4a inhibits cyclin-dependent kinase 4 CDK4 and cyclin-dependent kinase 6 CDK6, thus reinforcing the ability of the RB tumor suppressor to block cells in the G1 phase of the cell cycle. By contrast, p14ARF enhances the activity of the p53 tumor suppressor by inhibiting MDM2, an oncoprotein that stimulates p53 degradation. CDKN2A is mutated in approximately 10 of sporadic melanomas, and these mutations uniformly abolish the production of p16INK4a and more variably affect p14 ARF. However, it is suspected that these mutations are the tip of the oncogenic iceberg with respect to molec- ular lesions affecting the G1 checkpoint. For example, 30 to 70 of melanomas show loss of p16INK4a expression though varied mechanisms, and other famil- ial and sporadic melanomas have mutations in CDK4 