ABSTRACT
To develop into a uveal melanoma, melanocytes have to undergo genetic changes that enable these cells to re-enter the cell cycle and possibly at the same time repress apoptosis. As the size of the tumor increases, additional mutations can give tumor cells the potential to invade local barriers and to regulate their blood supply. Other mutations allow cells to enter the bloodstream, to extravasate elsewhere in the body, and to colonize these sites. All these changes are a result of random mutations, which will be selected for if they are beneficial to a tumor cell at some specific growth stage of the tumor. Chromosome-scale loss of genome integrity is usually a later event in many tumors, often related to the loss of p53. This may accelerate the rate of genetic changes acquired by tumor cells and thereby the progression to a malignant phenotype. A model for uveal melanoma oncogenesis predicts that three ratelimiting steps are required to develop a primary melanoma and a fourth to develop metastatic disease [1].
