CDKN2A and melanoma: It is not unreasonable to postulate that all pathogenic p53 mutations result from direct DNA damage from a mutagen, while loss of p16ink4a results from chronic oxidative stress, which may be due to ultraviolet A (melanoma), chronic inflammation (colon cancer, mesothelioma due to asbestos), viral oncogenesis (EBV), and other insults.12, 34, 35