BRAF kinase gene V599E mutation in growing melanocytic lesions

Abstract

Mutations in the BRAF-gene are found in benign and malignant melanocytic lesions, >90% being a V599E mutation. This mutation results in constitutively active kinase function and increased colony formation in vitro. The biological impact of this mutation in vivo is still debated. To address this question, we used our digital epiluminescence image archive and retrospectively selected 49 melanocytic lesions, which did not meet the criteria of melanoma at the initial presentation. Mean 12 months later these lesions were excised because of increased size or changed structure and BRAFV599E mutations were analysed. Among 36 growing lesions, BRAFV599E mutations were found in 16 (11 melanomas and 5 nevi). Among 13 lesions with structural changes, BRAFV599E mutations were found in 4 (3 melanomas and 1 nevus). Thirty-five randomly selected additional lesions with no changes during follow-up served as controls, all nevi by histology, and two of them showed a BRAFV599E mutation. Statistics revealed odds for the presence of the BRAFV599E mutation being seven times higher in lesions with structural changes and 13 times higher in growing lesions as compared with lesions without changes. This raises the question if the V5S9E mutation determines lesions at risk developing into melanoma and if not, what are the mechanisms controlling growth stop in benign lesions?