The TP53 tumor suppressor gene and melanoma tumorigenesis: is there a relationship?

Mutations in the TP53 gene are found in about 11% of melanomas. Although nearly 600 papers have been published with varying degrees of consensus, there does not appear to be any comparable analysis that facilitates more than a glimpse into the role of p53 in melanomagenesis. This article reviews p53 alterations (at the gene and protein levels) in melanocytic skin lesions and discusses the following points: (i) p53 alterations commence as early as at the stage of benign and dysplastic nevi; (ii) these alterations are frequent in melanomas, and gradually increase with their progression; (iii) there is no concordance between the frequent p53 protein expression and the rarity of both TP53 gene mutations in melanomas, and (iv) the entire p53 pathway is a more critical determinant of the fate of the melanocytic skin lesions than the status of the p53 protein or the gene itself.