Chromosomal translocations as a mechanism of BRAF activation in two cases of large congenital melanocytic nevi.

Genetic studies of melanocytic tumors have mainly demonstrated activation of oncogenes such as NRAS or BRAF through point mutations. In two cases of large congenital melanocytic nevi, we observed a chromosomal translocation involving the BRAF oncogene on chromosome 7q34, resulting in both cases in removal of the auto-inhibitory N-terminal regulatory domain (hence the Ras-guanosine triphosphate binding domain) of BRAF from its protein kinase domain. This is early evidence of BRAF activation through chromosomal translocation in melanocytic tumors. Because BRAF point mutations are rather rare in congenital melanocytic nevi and melanoma arising in non-sun-exposed area, the molecular mechanism of oncogenic activation as described here could be a recurrent molecular feature in these groups of melanocytic tumors.