Molecular Aspects of Melanoma

Dysregulation of the normal pathways of cell physiology is fundamental to carcinogenesis. Characterizing the changes that occur to the genes within these pathways will enhance understanding of how cancers arise and how they progress to advanced cancers, and it ultimately may lead to improved prognostication and treatment. Carcinogenesis is amultistep process, and typically, in order for a cell to becomemalignant, 4 to 7 rate-limiting stochastic genomic events occur. In most human cancers these events are incompletely characterized, and currently many crucial genetic changes are yet to be discovered. Malignant melanoma is one such example. A handful of “core” changes have been identified that make up a genetic signature that is common to most melanomas (Fig. 1), but beyond this, there are genetic changes that precede, accompany, or arise from the signature changes and account for the great phenotypic variation observed clinicopathologically. These “noncore” changes are also incompletely understood, but some potentially crucial mediators of melanoma development and progression have emerged. This discussion begins by describing signature changes in melanoma.