4.4 Article

BRAFV600E Mutation Status of Involuting and Stable Nevi in Dabrafenib Therapy With or Without Trametinib

Journal

JAMA DERMATOLOGY
Volume 150, Issue 10, Pages 1079-1082

Publisher

AMER MEDICAL ASSOC
DOI: 10.1001/jamadermatol.2014.436

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Funding

  1. National Health and Medical Research Council, Canberra, Australian Capital Territory, Australia [APP1004999]

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IMPORTANCE Recent advances in targeting BRAF(V600E) mutations, which occur in roughly 50% of melanomas and 70% of benign nevi, have improved response rates and survival in patients with melanoma. With increased survival, the importance of other comorbidities increases and requires consideration in long-term management. This case report discusses dynamic dermoscopic nevus changes that occur during dabrafenib therapy and offers some conclusions regarding BRAF mutations and the changes. OBSERVATIONS A man in his 30s had been monitored with whole-body dermoscopy at roughly 7-month intervals as part of a nevus surveillance study. Fourteen months after his initial visit, metastases were found, and the patient entered a clinical trial of dabrafenib with or without trametinib therapy. Continued dermoscopic monitoring for the next 12 months revealed that approximately 50% of the existing acquired melanocytic nevi involuted, while the remaining nevi did not change. Biopsy findings from 1 unchanged and 1 involuted nevus showed BRAF wild type in the unchanged nevus, BRAF(V600E) mutation in the involuting nevus, and no malignant histopathologic characteristics in either one. CONCLUSIONS AND RELEVANCE Our observations indicate that a previously suggested hypothesis regarding involuting nevi in BRAF inhibitor therapy is correct: Nevi that involute while a patient is undergoing BRAF(V600E) inhibitor therapy possess the BRAF(V600E) mutation, while others that grow or remain unchanged are wild type. However larger-scale trials are required to gather conclusive data and create a more complete clinical picture.

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