The presence of KIT proto-oncogene amplification and mutations in some melanoma subtypes provides an opportunity for treatment. In response, F. Stephen Hodi, MD, PhD, of the Dana-Farber Cancer Center, USA, and others conducted a study that examined imatinib in the treatment of metastatic mucosal, limbic, or chronic sun-damaged (CSD) melanoma in the presence of KIT amplification and/or mutations through a multicenter clinical phase II trial. In the study, patients were treated with once-daily doses of 400 mg of imatinib or, if initial remission was not achieved, twice daily doses of 400 mg of imatinib. Dose reductions were allowed in the event of treatment-related toxic events. Complementary proto-oncogene mutation screening was performed by mass spectrometry. The results of the study were published in the July 8, 2013 online issue of the Journal of ClinicalOncology. A total of 25 patients (24 of whom were evaluable) were recruited for the study. Eight patients (33%) had KIT mutations, 11 patients (46%) had KIT amplifications, and 5 patients (21%) had both KIT mutations and amplifications. The median follow-up of the study was 10.6 months (range, 3.7 months to 27.1 months). The best overall remission rate (BORR) was 29% (21% after exclusion of unvalidated remission events) with a bilateral 95% CI of 13% to 51%. the BORR was significantly higher than the false assumption of 5% and the BORR differed statistically significantly by mutation status (0% in 7 of 13 patients with KIT mutations or 54%v with KIT amplification only). There were no statistically significant differences between mutation status or melanoma sites in terms of progression rates or survival rates. The overall disease control rate was 50%, but control rates varied significantly by KIT mutation status (77% of mutated patients v 18% of amplified patients). four patients had NRAS mutations prior to treatment and one patient had enhanced KIT amplification after treatment. The authors of this study concluded that KIT mutation evaluation should be performed in mucosal, limbic or CSD cutaneous melanomas. Imatinib is effective in tumors with KIT mutations but not in tumors with KIT amplification only. In addition, the presence of NRAS mutations and increased KIT copy number may be the mechanism for the emergence of imatinib treatment resistance.