High frequency of BRAF mutations in nevi

Nat Genet. 2003 Jan;33(1):19-20. doi: 10.1038/ng1054. Epub 2002 Nov 25.


To evaluate the timing of mutations in BRAF (v-raf murine sarcoma viral oncogene homolog B1) during melanocytic neoplasia, we carried out mutation analysis on microdissected melanoma and nevi samples. We observed mutations resulting in the V599E amino-acid substitution in 41 of 60 (68%) melanoma metastases, 4 of 5 (80%) primary melanomas and, unexpectedly, in 63 of 77 (82%) nevi. These data suggest that mutational activation of the RAS/RAF/MAPK pathway in nevi is a critical step in the initiation of melanocytic neoplasia but alone is insufficient for melanoma tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Transformation, Neoplastic / genetics
  • DNA Mutational Analysis
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Humans
  • Melanoma / genetics*
  • Melanoma / pathology
  • Mutation, Missense / genetics*
  • Nevus / genetics*
  • Nevus / pathology
  • Oncogene Proteins v-raf / chemistry
  • Oncogene Proteins v-raf / genetics*
  • Polymerase Chain Reaction
  • Signal Transduction


  • Oncogene Proteins v-raf