Imatinib in Melanoma: A Selective Treatment Option Based on KIT Mutation Status?

Abstract

TO THE EDITOR: We read with great interest the article by Curtin et al 1 on activating KIT mutations in melanoma. The authors differentiate four subtypes of primary melanoma depending on sun exposureandlocalization:acralmelanoma,mucosalmelanoma,melanomaonchronicallysun-damagedskin,andmelanomaarisingfrom skin without signs of chronic sun damage. The latter subgroup has recently been shown to be characterized by frequent activating mutations in B-RAF and N-RAS, members of the MAP kinase pathway, whereas these mutations are rare in the other three subtypes. 2 In the current Curtin et al article, 1 these very same three subtypes were demonstratedtoholdhighfrequencies(28%to39%)ofgeneticaberrations in KIT, a receptor tyrosine kinase, whereas in contrast these aberrationswereabsent(0%)inmelanomasarisingfromskinwithout chronicsundamage. 1 ThedetectedKITaberrationsincludeddifferent mutations as well as copy number increases and were associated with an enhanced KIT protein expression. Eleven (69%) of 16 KIT mutations were predicted to affect the juxta-membrane domain, presumably resulting in a constitutive activation of KIT. These mutations are frequently found in gastrointestinal stromal tumors (GIST) and have beenshowntobehighlysensitivetoimatinib,atyrosinekinaseinhib