ANALYSIS OF RAS MUTATIONS IN HUMAN MELANOCYTIC LESIONS - ACTIVATION OF THE RAS GENE SEEMS TO BE ASSOCIATED WITH THE NODULAR TYPE OF HUMAN-MALIGNANT MELANOMA

We have analyzed the Ha-ras, Ki-ras and N-ras for point mutations at c odons 12, 13 and 61 via restriction fragment length polymorphism/polym erase chain reaction analysis and subsequent direct sequencing in non- cultured fresh-frozen tissues of 16 superficial spreading melanomas (S SM), 13 nodular malignant melanomas (NMM), 2 lentigo malignant melanom as (LMM), 1 dysplastic nevus, 1 congenital nevus and 5 normal nevi fro m 38 patients. Mutations were found in 4 melanoma samples, all belongi ng to the nodular malignant type. Three of them were mutated in N-ras and one in the Ha-ras gene. Mutation in N-ras was also detected in the congenital nevus. All mutations were exclusively located at the first two base pairs of codon 61. No Ki-ras mutation was detected in any le sion. No mutation could be found in SSM and LMM in addition to dysplas tic and normal nevi. The frequency of ras mutation in NMM was 31%, whe reas in SSM it was 0%. Our study suggests (a) an association between r as mutations (mainly N-ras) and the NMM as a subgroup of human melanom a; (b) that activation of Ki-ras is not involved in the pathogenesis o f melanoma. The role of UV radiation in point mutations of sas genes i n human melanoma is discussed.