Single genetic mutations can account for melanocytic naevi.
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.


OBJECTIVE
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.
Blewitt
R W
RW
Department of Pathology, Royal Lancaster Infirmary, Lancaster LA1 4RP, UK. robert.w.blewitt@rli.mbht.nhs.uk
D002455:Cell Division; D006801:Humans; D008544:Melanocytes / Q000473:pathology; D008957:Models, Genetic; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000473:pathology; D009508:Nevus, Pigmented / Q000151:congenital / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*