Activating mutations of the NRAS and BRAF genes occur in ∼20 and 50% of malignant melanomas respectively, and are almost always mutually exclusive (Omholt et al.,2003; Garnett and Marais,2004). BRAF and NRAS mutations have also been found in benign nevi (Poynter et al.,2006) and are therefore thought to be involved early in melanoma carcinogenesis. In cultured human melanocytes, mutant BRAF protein has been shown to induce cell senescence by increasing the expression of CDKN2A (Michaloglou et al.,2005). It is postulated, therefore, that to become an invasive melanoma, arrest of the cell cycle caused by normal CDKN2A must subsequently be overcome by mutation or deletion of CDKN2A or by alterations to other cell cycle regulators. Moreover, a recent in vitro study showed that simultaneous knockdown of BRAF and expression of CDKN2A in melanoma cells led to potent growth inhibition and apoptosis, whereas knockdown of BRAF or expression of CDKN2A alone did not (Zhao et al.,2008). Studies of BRAF mutated nevi using the senescence marker SA-β-gal, however, revealed a marked mosaic induction of CDKN2A, which the authors suggested was indicative of a role for multiple tumor suppressors in the prevention of BRAF oncogenesis (Michaloglou et al.,2005).