Mutational analysis of the N-ras, p53, p16(INK4a), CDK4, and MC1R genes inhuman congenital melanocytic naevi

Eighteen human congenital melanocytic naevi (CMN) from 17 patients were scr eened for activating point mutations in the oncogenes N-ras and CDK4 and fo r sequence variants in the MC1R gene by combined RFLP-PCR/SSCP analysis. In addition, all lesions were screened for deletions and point mutations in t he tumour suppressor genes p53 and p16(INK4a) (CDKN2A) by combined multiple x PCR/SSCP analysis. Positive screening data were specified by sequencing o f the corresponding PCR product. Activating point mutations in the N-ras ge ne (nine CAA (Gln) to AAA (Lys) transversions and one CAA (Gln) to CGA (Arg ) transition at codon 61) were detected at high frequency (56%). Furthermor e, three missense mutations (V92M) and two silent mutations (CGA (Arg) to C GG (Arg), codon 213, exon 6) were found in the MC1R and p53 genes, respecti vely. No mutations were found in pld or CDK4. The activated N-ras oncogene, which is also found in human cutaneous melanomas, may constitute a potenti al risk factor for melanoma formation within CMN.