Melanoma patients with a KIT mutation affecting a recurrent hot spot, such as the L576 or K642E mutation, had better clinical outcomes than those without a hotspot mutation, whereas those with a V654A or D820Y mutation, which are known to be associated with imatinib resistance in gastrointestinal stromal tumors, had early disease progression. In addition, melanoma patients with a mutant/wild-type allelic ratio of >1 had a higher response rate.

CONTRADICTING EVIDENCE: 69-year-old male with initial diagnosis of stage III-B melanoma of the left thumb with local recurrence in the resection site and then lung metastases...He was found to have KIT mutation (exon 13K642EMT), and started on imatinib, but he continued to have progression.