N-ras mutations are common in melanomas from sun-exposed skin of humans but rare in mucosal membranes or unexposed skin

J Invest Dermatol. 1998 Nov;111(5):757-61. doi: 10.1046/j.1523-1747.1998.00376.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Genes, ras / genetics*
  • Humans
  • Melanoma / genetics*
  • Mucous Membrane
  • Mutation
  • Neoplasms, Radiation-Induced / genetics*
  • Point Mutation
  • Polymorphism, Single-Stranded Conformational
  • Skin Neoplasms / genetics*
  • Ultraviolet Rays / adverse effects*