CDKN2A and metastatic neoplasm: The precise order of these events has not been determined for each aberrant melanocyte, but in a study by Shain et al. (68), it was found that UV-induced point mutations continued to increase, and invasive melanoma was associated with increased copy-number aberrations, particularly loss of CDKN2A. Further mutations and/or genomic aberrations (e.g., copy number gain/loss and promotor methylation) are necessary for the transition of locally invasive melanoma to metastatic disease and have been described in PTEN, AKT3, CDKN2A, CCND1, CDK4, RB1, TP53, MDM2, and ARID2 (Table 2) (65, 66, 70).