B-raf exon 15 mutations are common in primary melanoma resection specimens but not associated with clinical outcome

Oncology. 2004;66(5):411-9. doi: 10.1159/000079490.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cloning, Molecular
  • Electrophoresis
  • Exons
  • Humans
  • Melanoma / genetics*
  • Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins c-raf / genetics*
  • Skin Neoplasms / genetics*
  • Treatment Outcome


  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins c-raf