Ras mutations in human melanoma: a marker of malignant progression.
In this study we address whether there is an association between ras mutations and disease progression in malignant melanoma. DNA was extracted from 100 paraffin-embedded melanomas and sequences around the 12th, 13th and 61st codons of N-, H-, and K-ras were amplified using the polymerase chain reaction and probed for single base pair mutations using synthetic oligonucleotide probes. Thirty-six melanomas contained mutations, which in 25 cases (69%) occurred at the 61st codon of N-ras. The results from dot blot hybridizations were confirmed by subcloning and sequencing the polymerase chain reaction products from two tumors. No ras mutations were found in Clark's level I melanomas, whereas 19% of level II and 45% of the more advanced primary tumors contained ras mutations (Chi squared test: p < 0.05). The median Breslow thickness of primary melanomas with ras mutations was 0.72 mm, significantly thicker than the 0.42 mm of melanomas without mutations (Mann-Whitney U test, p = 0.042). Ras mutations were found more frequently in primary tumors from continuously exposed skin (56%) than tumors from intermittently or non-sun exposed sites (21%). Fifty percent of locally recurrent and 47% of metastatic melanomas had ras mutations. We conclude that ras mutations occur in a subset of melanomas from sun-exposed skin as a feature of tumor progression.
Ball
N J
NJ
Department of Dermatology, University of Colorado Health Sciences Center, Denver 80262.
Yohn
J J
JJ
Morelli
J G
JG
Norris
D A
DA
Golitz
L E
LE
Hoeffler
J P
JP
D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization / Q000379:methods; D008545:Melanoma / Q000235:genetics*; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000235:genetics; D016133:Polymerase Chain Reaction; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects