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March 1, 2017

BRAF V600E Mutation in Involuting Nevus in a Patient Treated With Vemurafenib

Author Affiliations
  • 1Dermatology Department, Hospital Costa del Sol, Marbella, Spain
  • 2Pathology Department, Hospital Costa del Sol, Marbella, Spain
JAMA Dermatol. Published online March 1, 2017. doi:10.1001/jamadermatol.2016.6091

Vemurafenib is considered a first-line treatment for unresectable or metastatic malignant melanoma (MM) with V600E mutation of the BRAF gene (OMIM 155600). Among its many adverse effects are regressive changes, the development of increasing atypia in preexisting nevi, and the appearance of second melanomas.14 Increasing atypia can be explained by a paradoxical pathway activation of mitogen-activated protein (MAP) kinases in cells with no mutation.1 This process would also account for the appearance of second, wild-type, melanomas. It has been hypothesized that changes in the nevi with regression are caused by the presence of mutated nevus cells, which respond to treatment in the same way as those of the primary MM.2 However, to our knowledge, this hypothesis has been corroborated by only 1 study,5 which reported the case of a patient treated with dabrafenib for a metastatic MM who developed regressive changes in some nevi. The nevus cells of the involuting lesions presented the same mutation.5

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