NRAS and BRAF mutations in atypical melanocytic lesions arising in melanoma patients treated with vemurafenib.

9017 Background: BRAF inhibition with targeted therapy has demonstrated improved overall survival in patients with BRAF mutant melanoma. The use of the selective BRAF inhibitors vemurafenib and dabrafenib are associated with a range of known and predictable cutaneous side effects, including squamous cell carcinomas often associated with RAS mutations. Preclinical evidence indicates that BRAF inhibitors may give rise to non-melanoma tumors by promoting MAPK activation in the tissues that lack mutant BRAF. Here we report atypical melanocytic lesions arising in patients treated with the BRAF inhibitor vemurafenib. Methods: To characterize the mutations of both the melanoma tumors and the atypical melanocytic lesions arising in patients with BRAF V600E/K melanoma treated with vemurafenib, a custom Sequenom panel designed to detect 74 mutations in 12 genes known to play a role in the pathogenesis of melanoma was applied to both melanoma and atypical melanocytic lesions for each patient. Results: We observed a ...