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[Cancer Research 63, 3955-3957, July 15, 2003]
© 2003 American Association for Cancer Research

Clinical Investigations

Analysis of BRAF and N-RAS Mutations in Metastatic Melanoma Tissues1

Alexis Gorden, Iman Osman, Weiming Gai, Dan He, Weiqing Huang, Anne Davidson, Alan N. Houghton, Klaus Busam and David Polsky2

Ronald O. Perelman Department of Dermatology [A. G., I. O., W. G., D. H., D. P.], Kaplan Comprehensive Cancer Center [I. O.], New York University School of Medicine, New York, New York 10016; Departments of Medicine and Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461 [W. H., A. D.]; and Memorial Sloan-Kettering Cancer Center, New York, New York 10024 [A. N. H., K. B.]

We examined mutations in BRAF exons 11 and 15 and N-RAS exons 2 and 3, in 77 metastatic melanoma cases and 11 melanoma cell lines. Significant differences in the mutation rates observed at different metastatic sites could not be detected. The most frequent mutation, the V599E amino acid substitution in BRAF exon 15, was observed in 31 of 77 (40%) tissues and 5 of 11 (45%) cell lines. Tandem base-pair substitutions encoding V599R and V599K amino acid changes were observed in two cases. Novel findings with respect to melanoma include a cell line possessing a 2 base-pair substitution in BRAF exon 11 and a case harboring mutations in both BRAF exon 11 and N-RAS exon 3. Our data show that BRAF mutation is common in melanoma metastases, regardless of their site, that mutations include both exons 11 and 15, and suggest that anti-RAS/RAF strategies may be effective in metastatic melanoma patients.




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Copyright © 2003 by the American Association for Cancer Research.