Point mutations in the N-ras oncogene in malignant melanoma and congenital naevi.
DNA from formalin-fixed and paraffin-processed samples from 100 melanocytic lesions (39 malignant melanomas, 18 cases of dysplastic naevi, and 43 congenital naevi) was extracted, and the sequences around codons 12/13 and 61 of the N-ras oncogene were amplified using the polymerase chain reaction. The amplified product was then analysed both by dot-blotting and by direct sequencing for point mutations. By the dot-blotting technique, mutations were seen in 18 of 100 lesions. These were in one of five distant metastases (20%), in one of three nodal metastases (33%), in four of 31 (13%) primary melanomas, in none of 18 dysplastic naevi, and in 12 of 43 (28%) congenital naevi, all at codon 61. On direct sequencing, nine of 18 mutations were confirmed, in two of 31 (6%) primary tumours, one distant metastasis, and six of 43 (14%) congenital naevi. Of the 23 superficial spreading melanomas examined, eight were on sun-exposed skin. A superficial spreading melanoma, in which the N-ras mutation at codon 61 was confirmed, was on non-exposed skin, and an unconfirmed mutation was from an exposed site. One of three nodular melanomas with a confirmed mutation was on a light-exposed site, and the other two nodular melanomas were from non-exposed areas. All four lentigo maligna melanomas were from exposed sites, and one of these had an unconfirmed mutation. The only acral lentiginous melanoma, which had no mutation, was from a sun-exposed area.(ABSTRACT TRUNCATED AT 250 WORDS)
Carr
J
J
Department of Dermatology, University of Glasgow, U.K.
Mackie
R M
RM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D003062:Codon / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004416:Dysplastic Nevus Syndrome / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D005821:Genetic Techniques; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009506:Nevus / Q000235:genetics*; D009508:Nevus, Pigmented / Q000151:congenital / Q000235:genetics; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000151:congenital / Q000235:genetics*
D003062:Codon; D017931:DNA Primers