N-ras mutations are common in melanomas from sun-exposed skin of humans but rare in mucosal membranes or unexposed skin.
Ras mutations, preferentially in codon 61 of the N-ras oncogene, are common in human cutaneous melanomas. In this study, we questioned the association between ras mutations in primary melanomas and sun exposure. DNA was extracted from formalin-fixed primary melanomas: 28 at chronically sun-exposed head and neck areas, 18 at sites subject to intermittent sun exposure, and 28 from unexposed mucosal membranes (vulva/vagina, anus/ rectum, palate). Mutations of both exons of H-, K-, and N-ras genes were examined by polymerase chain reaction/single-strand conformation polymorphism and by direct nucleotide sequencing of the polymerase chain reaction amplified exons. Thirty-two per cent of the head and neck melanomas and 11% of the melanomas from intermittently sun-exposed skin had N-ras codon 61 mutations; comparatively only 7% of the tumors from the unexposed areas had such mutations. One vulvar melanoma had an N-ras codon 12 mutation. No H-ras or K-ras mutations were detected in any sample. The frequency of N-ras exon 2 mutations in melanomas of typically sunbathed skin was compared for the first time with that in melanomas of areas completely protected from sun exposure. The significantly higher frequency (p = 0.04, chi square exact test) of these N-ras mutations on the head and neck demonstrates their UV-light induction in a subset of melanomas explaining one of the molecular effects of UV light in human skin.
Jiveskog
S
S
Department of Oncology, Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Ragnarsson-Olding
B
B
Platz
A
A
Ringborg
U
U
D001483:Base Sequence; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D009092:Mucous Membrane; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012878:Skin Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays / Q000009:adverse effects*