| Ha et al., recently used a mouse model to demonstrate that p14ARF but not p53, suppressed early melanomagenesis and operated independent of p53 to induce melanocyte senescence. This added benefit of p14ARF loss may help explain why CDKN2A, as opposed to p53, is preferentially abrogated in melanoma. CDKN2A expression changes were identified in the vast majority of melanomas through mutation, deletion or promoter hypermethylation of CDKN2A gene. CDKN2A harbors mutations in melanoma at dipyrimidine sites but many of these genetic alterations are not UVB signature mutations. An ongoing trial is aimed to identify gene mutations in patients with melanoma and in families with a history of hereditary melanoma and monitors for CDKN2A mutations. Restoring function of a lost or defective gene in cancer has generally proven to be more difficult than blocking a hyperfunctional gene; thus it is not surprising that most efforts in targeted melanoma therapy have focused on suppression of oncogene signaling rather than TSG restoration.