How is molecular pathogenesis of melanoma?

➢ Note that no melanocytic nevus precursor is identified in most cases of melanoma. ➢ They are believed to arise de novo, perhaps all using the same pathway. ➢ The initiating event appears to be an activating mutation in BRAF or (less commonly) RAS. ➢ This, usually, produces only a benign nevus unless other mutations are superimposed. ➢ Sequencing of nevi with “atypical” morphologic features suggestive of melanoma as well as melanomas in the radial phase of growth (melanoma in situ) has shown that they commonly harbor mutations that activate the expression of telomerase.