The aim of this study was to assess the prevalence of clinically significant somatic mutations, specifically BRAF, NRAS and KIT, in a large cohort of Australian patients with metastatic melanoma.
Baseline and 4-week follow-up 18F-FDG-PET/CT were evaluated in 17 patients with metastatic melanoma and KIT amplifications and/or mutations treated with imatinib in a multicenter phase II clinical trial.
Some recurrent KIT mutations are well characterized; others are poorly described.OBSERVATIONS We describe a novel KIT mutation in a patient with metastatic melanoma.
These mutations have become clinically relevant for targeted therapy of patients with advanced disease, especially for the treatment of patients with metastatic melanoma carrying the BRAF(V600) or KIT mutations.
Given its favorable safety and efficacy profile in CML and imatinib-resistant GISTs, nilotinib, a second-generation tyrosine kinase inhibitor with greater potency than imatinib, emerges as a promising agent in the treatment of metastatic melanoma harboring the KIT mutation and warrants clinical investigation in this setting.
Recently 12 cases of metastatic melanoma and KIT-activating mutations have been published to be successfully treated with c-KIT blockers such as imatinib, sunitinib, dasatinib or sorafenib.
More recently, activating KIT mutations have been described in rare cases of metastatic melanoma, without further reference to their clinical phenotypes.
The CD117 immunoreactivity may prove useful in the differential diagnosis of deep soft tissue or visceral lesions with melanocytic differentiation; positive staining results exclude clear cell sarcoma, but are compatible with metastatic melanoma.