Analysis ofrasmutations in human melanocytic lesions: activation of therasgene seems to be associated with the nodular type of human malignant melanoma

Autor: Jafari, Mehrdad, Papp, Thilo, Kirchner, Stephan, Kiener, Ulrike, Henschler, Dietrich, Burg, Günter, Schiffmann, Dietmar
Zdroj: Journal of Cancer Research and Clinical Oncology; January 1995, Vol. 121 Issue: 1 p23-30, 8p
Abstrakt: We have analyzed the Ha-ras, Ki-rasand N-rasgene for point mutations at codons 12, 13 and 61 via restriction fragment length polymorphism/polymerase chain reaction analysis and subsequent direct sequencing in non-cultured fresh-frozen tissues of 16 superficial spreading melanomas (SSM), 13 nodular malignant melanomas (NMM), 2 lentigo malignant melanomas (LMM), 1 dysplastic nevus, 1 congenital nevus and 5 normal nevi from 38 patients. Mutations were found in 4 melanoma samples, all belonging to the nodular malignant type. Three of them were mutated in N-rasand one in the Ha-rasgene. Mutation in N-raswas also detected in the congenital nevus. All mutations were exclusively located at the first two base pairs of codon 61. No Ki-rasmutation was detected in any lesion. No mutation could be found in SSM and LMM in addition to dysplastic and normal nevi. The frequency ofrasmutation in NMM was 31%, whereas in SSM it was 0%. Our study suggests (a) an association betweenrasmutations (mainly N-ras) and the NMM as a subgroup of human melanoma; (b) that activation of Ki-rasis not involved in the pathogenesis of melanoma. The role of UV radiation in point mutations ofrasgenes in human melanoma is discussed.
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