KIT in melanoma: many shades of gray.

Activating mutations in KIT have been identified in melanomas of acral and mucosal types and in those arising in chronically sun-damaged skin. Until now, KIT has been considered an oncogenic driver and a potential therapeutic target. However, data presented by Dhal et al. show that in cutaneous melanomas the KIT promoter is a target for hypermethylation, leading to its downregulation. Their observations suggest that signaling pathways downstream of KIT may have distinct and opposing roles in the pathogenesis of melanoma subtypes. This will have important implications for the use of KIT inhibitors in treating melanomas.