SHORT REPORT

Absence of BRAF mutations in UV-protected mucosal melanomas

R H Edwards¹, M R Ward¹, H Wu², C A Medina¹, M S Brose¹, P Volpe¹, S Nussen-Lee³, H M Haupt³, A M Martin³, M Herlyn⁴, S R Lessin², B L Weber¹

¹ Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA
² Fox Chase Cancer Center, Philadelphia, PA, USA
³ Pennsylvania Hospital, Philadelphia, PA, USA
⁴ The Wistar Institute, Philadelphia, PA, USA

Correspondence to:
Correspondence to:
B L Weber
MD, Abramson Family Cancer Research Institute, University of Pennsylvania Medical Center, 514 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA; weberb{at}mail.med.upenn.edu

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.

Keywords: BRAF; melanoma; ultraviolet exposure

Abbreviations: CPD, cyclobutane pyrimidine dimers; RFLP, restriction fragment length polymorphism; UV, ultraviolet

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