Absence of BRAF mutations in UV-protected mucosal melanomas. Issue 4 (1st April 2004)

• Record Type: Journal Article
• Authors: Edwards, R H; Ward, M R; Wu, H; Medina, C A; Brose, M S; Volpe, P; Nussen-Lee, S; Haupt, H M; Martin, A M; Herlyn, M; Lessin, S R; Weber, B L
• Is Part Of: Journal of medical genetics. Volume 41:Issue 4(2004)
• Page Start: 270
• Page End: 272
• Publication Date: 2004-04-01
• Subjects: BRAF -- melanoma -- ultraviolet exposure; CPD, cyclobutane pyrimidine dimers -- RFLP, restriction fragment length polymorphism -- UV, ultraviolet; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmg.2003.016667
• Languages: English
• ISSNs: 1468-6244

Abstract

Abstract : Background: Mutations in BRAF have recently been identified in a significant percentage of primary and metastatic cutaneous malignant melanomas. As ultraviolet (UV) exposure may play a role in the development of cutaneous melanoma lesions with BRAF mutations, BRAF mutation frequency in melanomas arising in sites protected from sun exposure may be lower than those from sun-exposed areas. Thus, we determined the BRAF mutation frequency in a panel of 13 mucosal melanomas and compared those data with data from all currently published series of cutaneous melanomas. Methods: BRAF exon 15 DNA from 13 archival primary mucosal melanomas (eight vulvar, four anorectal, and one laryngeal) was sequenced using intron-based primers. As archival DNA occasionally produces poor-quality template, results were confirmed with a TspRI restriction fragment length polymorphism (RFLP) that distinguishes wild-type BRAF from the common mutant form V599E. A binomial test was used to compare the mutation frequency in the mucosal melanomas with the published mutation frequency in cutaneous melanomas. Results: None of the 13 mucosal melanomas in this series had an exon 15 BRAF mutation, as compared to 54/165 (33%) primary cutaneous melanomas with BRAF mutations in a compilation of all current published studies (p = 0.006). Discussion: These data suggest that UV exposure, plays a role in the genesis of BRAF mutations in cutaneous melanoma, despite the absence of the characteristic C>T or CC>TT mutation signature associated with UV exposure, and suggests mechanisms other than pyrimidine dimer formation are important in UV-induced mutagenesis.