Earlier studies have shown frequent mutations in the BRAF and NRAS genes in 
cutaneous melanoma, but these alterations have not been examined in the rare 
category of melanoma from black Africans. Moreover, the frequency of epidermal 
growth factor receptor (EGFR) mutations in melanocytic tumors is not known. We 
therefore examined 165 benign and malignant melanocytic lesions (including 118 
invasive melanomas and 18 metastases collected as consecutive cases from various 
time periods and from two different pathology departments; the 51 nodular 
melanomas were randomly selected from a larger, consecutive, population-based 
series of nodular melanomas) with respect to alterations in the EGFR, BRAF and 
NRAS genes. Mutations in EGFR (exons 18-21) were not detected. EGFR protein 
expression was observed in a subgroup of melanomas, but without associations 
with clinicopathologic phenotype or prognosis. Cytoplasmic EGFR expression was, 
however, significantly increased from benign nevi to melanomas. Mutations in 
BRAF and NRAS were detected in superficial melanoma (25 and 29%, respectively), 
nodular melanoma (29 and 28%, respectively) and lentigo maligna melanoma (15 and 
16%, respectively). In a series of melanomas from black Africans (n=26), only 
two BRAF mutations (8%) were found, both being different from the common T1799A 
substitution. Moreover, melanomas from black Africans exhibited mutations in 
NRAS exon 1 only (12%), whereas NRAS exon 2 mutations were predominant in 
melanomas from Caucasians. Thus, the frequencies of BRAF and NRAS mutations were 
particularly low in melanomas from black Africans, supporting a different 
pathogenesis of these tumors.