Single genetic mutations can account for melanocytic naevi

Abstract

Background: The nature of melanocytic naevi is unknown notwithstanding their considerable significance for clinician and pathologist and despite the wealth of existing knowledge about melanocyte biology. Objectives: To investigate how far a simple mutational model can explain the clinical and pathological features of melanocytic naevi, in particular their pattern of onset and frequency. Methods: I have constructed a model of the development of the adult melanocyte population from a single stem cell. The total cutaneous melanocyte population in a human adult is already known, as well as the range of spontaneous mutation rates at a given gene site. For each cycle of mitosis during the post stem-cell expansion of the melanocyte population, I calculate the accumulated number of cells likely to be mutated at a particular (although unknown) gene site. The results are interpreted in the light of a hypothesis that each of these mutant melanocytes will go on to form a melanocytic naevus. Comparisons are made with neurofibromas, occurring in type 1 neurofibromatosis and as sporadic lesions. Results: A single genetic mutation in melanocyte precursors is found to be sufficient to explain the clinical and pathological features of melanocytic naevi. Conclusions: I propose that melanocytic naevi are a consequence of single spontaneous genetic mutations which inevitably occur during the development of the adult population of cutaneous melanocytes. © 2005 British Association of Dermatologists.