Distribution of BRAF T1799A(V600E) Mutations Across Various Types of Benign Nevi: Implications for Melanocytic Tumorigenesis

Abstract

PURPOSE: The BRAF mutation is common in melanomas, but variation in rates across melanoma subtypes points to a complex interplay between BRAF activation and other factors (eg, sun exposure). Nevi also harbor the BRAF mutation. A description of mutation distribution in nevi could provide insight into the significance of this event in melanocytic tumorigenesis. EXPERIMENTAL DESIGN: One hundred thirty-five nevi from 116 patients were evaluated for the T-->A mutation at nucleotide 1799. The nevi were inclusive of congenital (n = 34) and acquired (n = 101) nevi, dysplastic (n = 11) and nondysplastic (n = 124) nevi, and anogenital (n = 24) and common cutaneous (n = 111) nevi. RESULTS: The overall mutation rate was 81%. The rate varied only slightly by anatomic site: BRAF mutations were detected in 21 of 21 (100%) nevi of the head and neck, 62 of 76 (82%) nevi of the trunk, 8 of 14 (62%) nevi of the extremities, and 18 of 24 (75%) anogenital nevi. For acquired nevi, there was no association between BRAF mutations and sun exposure as inferred from anatomic site. There were no significant differences in the mutation rates between congenital and acquired nevi (76% versus 81%; P = 0.5). CONCLUSIONS: The BRAF mutation is uniformly distributed in various types of nevi. Its presence in congenital and anogenital nevi points to mechanisms of induction other than sun exposure. Its ubiquitous presence suggests that it poses no significant threat of malignant transformation, raising doubts about its relevance in melanoma development and its suitability as a target of directed therapy in patients with melanoma.