Exclusion of BRAFV599E as a melanoma susceptibility mutation

Int J Cancer. 2003 Aug 10;106(1):78-80. doi: 10.1002/ijc.11199.


Very recently, BRAF mutations were found in about 2/3 of malignant melanomas and at lower frequencies in other human cancers. The BRAF gene codes for a protein in the mitogen-activated protein kinase (MAPK) pathway. All mutations identified to date are within the kinase domain, with a single missense mutation (V599E) accounting for 80%. We investigated the hypothesis that this common somatic BRAF mutation (V599E) would contribute to melanoma predisposition in familial and polygenic malignant melanoma if occurring as a germ-line mutation. We performed comprehensive mutational screening of exon 15 of BRAF using DHPLC (denaturing high-performance liquid chromatography) and DNA sequencing techniques. No V599E mutation could be detected in 172 melanoma patients comprising 46 familial cases, 21 multiple melanoma patients and 106 cases with at least one first-degree relative suffering from other cancers. We therefore conclude that the common somatic BRAF mutation V599E does not contribute to polygenic and familial melanoma predisposition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Chromatography, High Pressure Liquid
  • DNA Mutational Analysis*
  • Exons
  • Genetic Predisposition to Disease*
  • Genotype
  • Heterozygote
  • Humans
  • MAP Kinase Signaling System
  • Melanoma / genetics*
  • Mutation*
  • Mutation, Missense
  • Pedigree
  • Time Factors