RAS Mutations in Human Melanoma: A Marker of Malignant Progression
| Autor: | Nigel J. Ball, David A. Norris, James P. Hoeffler, Joseph G. Morelli, Joseph J. Yohn, Loren E. Golitz |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Pathology
medicine.medical_specialty Neoplasms Radiation-Induced Time Factors Ultraviolet Rays polymerase chain reaction Immunoblotting Dot blot Dermatology Biology medicine.disease_cause Biochemistry law.invention 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine law medicine Humans DNA sequencing Melanoma Gene Molecular Biology In Situ Hybridization Polymerase chain reaction 030304 developmental biology 0303 health sciences Mutation Cell Biology medicine.disease 3. Good health Genes ras Subcloning chemistry Tumor progression 030220 oncology & carcinogenesis mismatch hybridization Cancer research DNA |
| Zdroj: | Journal of Investigative Dermatology. 102(3):285-290 |
| ISSN: | 0022-202X |
| DOI: | 10.1111/1523-1747.ep12371783 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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