B-raf exon 15 mutations are common in primary melanoma resection specimens but not associated with clinical outcome.
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.
Deichmann
Martin
M
Department of Dermatology, University Clinics of Heidelberg, Heidelberg, Germany. martin_deichmann@med.uni-heidelberg.de
Thome
Marianne
M
Benner
Axel
A
Näher
Helmut
H
D003001:Cloning, Molecular; D004586:Electrophoresis; D005091:Exons; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D016896:Treatment Outcome
D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf