B-raf Exon 15 Mutations Are Common in Primary Melanoma Resection Specimens but Not Associated with Clinical Outcome
| Autor: | Martin Deichmann, Axel Benner, Helmut Näher, Marianne Thome |
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| Rok vydání: | 2004 |
| Předmět: | |
| Zdroj: | Oncology. 66:411-419 |
| ISSN: | 1423-0232 0030-2414 |
| DOI: | 10.1159/000079490 |
| Popis: | Downstream of Ras, the serine/threonine kinase B-raf has recently been reported to be mutated, among other carcinomas, in a majority of melanoma cell lines with a preponderance of mutations within the kinase domain including the activating V599E transition. We therefore investigated a representative number of 50 primary melanoma resection specimens for the presence of mutations within the activation segment (exon 15) of the B-raf kinase domain. Applying polymerase chain reaction and single-strand conformation polymorphism gel electrophoresis, followed by DNA cloning and sequencing, we found 19 cases (38%) to harbor somatic B-raf exon 15 mutations. With respect to the B-raf protein sequence, the V599E mutation was predicted in 63% of these positive melanomas, followed in frequency by the V599K transition (31%). Detection of B-raf exon 15 mutations or prediction of the activating mutation V599E were not statistically associated with the risk for subsequent metastasis in the follow-up of patients. Altogether, the B-raf oncogene is affected in a substantial subset of melanoma resection specimens. As B-raf alterations possibly affect melanocyte-specific pathways controlling proliferation and differentiation, activation of this oncogene may contribute to the development of melanoma. |
| Databáze: | OpenAIRE |
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