© 2003 by Oxford University Press
© 2003 Oxford University Press
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Determinants of BRAF Mutations in Primary Melanomas
Affiliations of authors: Departments of Dermatology (JLM, BCB), Laboratory Medicine (JF, ANJ, DGA, DP), and Pathology (BCB), Cancer Research Institute (JF, ANJ, DGA), Comprehensive Cancer Center (HP, ANJ, DGA, DP, BCB), University of California, San Francisco, San Francisco; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY (KB); Department of Dermatology, Kumamoto University School of Medicine, Kumamoto, Japan (TK, TO).
Correspondence to: Boris C. Bastian, MD, Department of Dermatology and Pathology, University of California, San Francisco, 2340 Sutter St., Rm. N461, San Francisco, CA 94115 (e-mail: bastian{at}cc.ucsf.edu)
The RAS/mitogen-activated protein kinase pathway sends external growth-promoting signals to the nucleus. BRAF, a critical serine/threonine kinase in this pathway, is frequently activated by somatic mutation in melanoma. Using a cohort of 115 patients with primary invasive melanomas, we show that BRAF mutations are statistically significantly more common in melanomas occurring on skin subject to intermittent sun exposure than elsewhere (23 of 43 patients; P<.001, two-sided Fisher’s exact test). By contrast, BRAF mutations in melanomas on chronically sun-damaged skin (1 of 12 patients) and melanomas on skin relatively or completely unexposed to sun, such as palms, soles, subungual sites (6 of 39 patients), and mucosal membranes (2 of 21 patients) are rare. We found no association of mutation status with clinical outcome or with the presence of an associated melanocytic nevus. The mutated BRAF allele was frequently found at an elevated copy number, implicating BRAF as one of the factors driving selection for the frequent copy number increases of chromosome 7q in melanoma. In summary, the uneven distribution of BRAF mutations strongly suggests distinct genetic pathways leading to melanoma. The high mutation frequency in melanomas arising on intermittently sun-exposed skin suggests a complex causative role of such exposure that mandates further evaluation.
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Correspondence about this Article
- Re: Determinants of BRAF Mutations in Primary Melanomas
- Mark P. Purdue
J Natl Cancer Inst 2005 97: 401-402.[Extract] [Full Text] [PDF]
- RESPONSE: Re: Determinants of BRAF Mutations in Primary Melanomas
- J. L. Maldonado, J. Fridlyand, and B. C. Bastian
J Natl Cancer Inst 2005 97: 402.[Extract] [Full Text] [PDF]
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