Causes, consequences and clinical significance of aneuploidy across melanoma subtypes

Aneuploidy, the state of the cell in which the number of whole chromosomes or chromosome arms becomes imbalanced, has been recognized as playing a pivotal role in tumor evolution for over 100 years. In melanoma, the extent of aneuploidy, as well as the chromosomal regions that are affected differ across subtypes, indicative of distinct drivers of disease. Multiple studies have suggested a role for aneuploidy in diagnosis and prognosis of melanomas, as well as in the context of immunotherapy response. A number of key constituents of the cell cycle have been implicated in aneuploidy acquisition in melanoma, including several driver mutations. Here, we review the state of the art on aneuploidy in different melanoma subtypes, discuss the potential drivers, mechanisms underlying aneuploidy acquisition as well as its value in patient diagnosis, prognosis and response to immunotherapy treatment.