Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Armstrong, B.K. & English, D.R. in Cancer Epidemiology and Prevention (Oxford University Press, New York, 1996).
Elder, D.E. & Murphy, G.F. in Atlas of Tumor Pathology: Melanocytic Tumors of the Skin 5–101 (Armed Forces Insititute of Pathology, Washington, DC, 1991).
Davies, H. et al. Nature 417, 949–954 (2002).
Halaban, R. Pigment Cell Res. 13, 4–14 (2000).
Busca, R. et al. EMBO J. 19, 2900–2910 (2000).
Kononen, J. et al. Nat. Med. 4, 844–847 (1998).
Acknowledgements
Special thanks to S. Rosenberg for providing the melanoma samples for the tissue array, R. Bonner and M. Mertts for the use of their Leica AS LMD Microscope and for advice regarding laser microdissection and D. Leja for assistance preparing figures. This work was supported in part by a grant from the Queensland Cancer Fund and the US National Institutes of Health (N.K.H. and M.S.) and an Australian National Health and Medical Research Council C.J. Martin Fellowship (to P.M.P.). These studies were approved by the institutional review boards of both Queensland Institute of Medical Research and the National Human Genome Research Institute, US National Institutes of Health. The National Human Genome Research Institute Institutional Review Board has approved the use of previously collected, stored tissue samples, which remain anonymous to protect individuals' confidentiality.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Pollock, P., Harper, U., Hansen, K. et al. High frequency of BRAF mutations in nevi. Nat Genet 33, 19–20 (2003). https://doi.org/10.1038/ng1054
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ng1054
- Springer Nature America, Inc.
This article is cited by
-
Alternative Wnt-signaling axis leads to a break of oncogene-induced senescence
Cell Death & Disease (2024)
-
Runx1/3-driven adaptive endoplasmic reticulum stress pathways contribute to neurofibromagenesis
Oncogene (2023)
-
The genomic landscape and clonal evolutionary trajectory of classical hairy cell leukemia
Leukemia (2023)
-
The journey from melanocytes to melanoma
Nature Reviews Cancer (2023)
-
Clinical features, molecular pathology, and immune microenvironmental characteristics of acral melanoma
Journal of Translational Medicine (2022)