Distinct sets of genetic alterations in melanoma

Conclusions

Acral and mucosal primary melanomas had greater similarities in molecular findings than did the two types of skin sites. Melanomas that occur on chronically sun-damaged skin share with nonmelanoma skin cancers the presence of extensive ultraviolet light-induced DNA damage. Those that arise in skin with intermittent sun exposure are commonly found in subjects with more moles, fewer solar keratoses, younger age, more likely association with family history, and the highest incidence of BRAF mutation. It is hypothesized that susceptibility to melanomas of this type is site-specific and depends on a temporal (early in life) “window of vulnerability” to ultraviolet light exposure. In contrast, melanomas that arise in the setting of chronic sun damage require more cumulative ultraviolet exposure to cause sufficient damage for melanomagenesis. The authors believe, based on some subset features from samples used in this study, that the distinctions among the four traditional types of melanoma (see previous text) are far less important than the categories defined by the genetic findings of this study. They go on to propose that the aberrant pathways associated with each of the four groups distinguished by their molecular features in this study will provide therapeutic targets for new agents in development.