The prevalence of BRAF and NRAS in dermoscopic subtypes of acquired naevi

Constitutive activation of the mitogen-activated protein kinase (MAPK) pathway resulting in cell growth promotion is most commonly implicated in melanoma development and involves mutation of mutually exclusive BRAF or NRAS. The dual pathway of naevogenesis proposed to give rise to globular and reticular dermoscopic subtypes of acquired naevi may help to explain the relative melanoma risks posed by naevi.1 Furthermore acquired naevi with a peripheral rim of globules exhibit symmetrical enlargement over time, an implication that growth does not always indicate malignant transformation.2 We assessed the BRAF and NRAS mutant frequency in 40 acquired naevi with globular (n=13), reticular (n=15) and peripheral rim of globules (n=12) patterns using droplet digitalTM PCR. This highly sensitive mutation detection method reveals BRAF in 92.3% of globular naevi (n=12/13), 66.7% of reticular naevi (n=10/15) and 100% of naevi with a peripheral rim of globules (n=12/12). NRAS was detected in 7.7% of globular naevi (n=1/13) and 33.3% of reticular naevi (n=5/15). As activation of the MAPK pathway was observed in 100% of the analysed acquired naevi, this suggests that BRAF and NRAS mutations constitute key early somatic events in the development of acquired naevi and that mutation of other candidate genes are required for melanomagenesis.
1. Zalaudek I, Hofmann-Wellenhof R, Kittler H, et al. A dual concept of naevogenesis: theoretical considerations based on dermoscopic features of melanocytic naevi. JDDG. 2007; 5(11): 985-992
2. Bajaj S, Dusza SW, Marchetti MA, et al. Growth-curve modelling of naevi with a peripheral globular pattern. JAMA Dermatol. 2015; 151(12): 1338-1345

Dr. Jean-Marie Tan