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JNCI J Natl Cancer Inst
Year: 2009  |  Volume: 101  |  Issue: 20  |  Page No.: 1423 - 1427

Polyclonality of BRAF Mutations in Acquired Melanocytic Nevi

J Lin, M Takata, H Murata, Y Goto, K Kido, S Ferrone and T. Saida    

Abstract:

Melanocytic nevi are thought to be senescent clones of melanocytes that have acquired an oncogenic BRAF mutation. BRAF mutation is considered to be a crucial step in the initiation of melanocyte transformation. However, using immunomagnetic separation or laser-capture microdissection, we examined BRAF mutations in sets of approximately 50 single cells isolated from acquired melanocytic nevi from 13 patients and found a substantial number of nevus cells that contained wild-type BRAF mixed with nevus cells that contained BRAFV600E. Furthermore, we simultaneously amplified BRAF exon 15 and a neighboring single nucleotide polymorphism (SNP), rs7801086, from nevus cell samples obtained from four patients who were heterozygous for this SNP. Subcloning and sequencing of the polymerase chain reaction products showed that both SNP alleles harbored the BRAFV600E mutation, indicating that the same BRAFV600E mutation originated from different cells. The polyclonality of BRAF mutations in acquired melanocytic nevi suggests that mutation of BRAF may not be an initial event in melanocyte transformation.

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