Determination of the BRAF V600E mutation in Uruguayan melanoma patients.

Abstract

e19007 Background: Vemurafenib approval by the FDA determines a new era for the treatment of metastatic melanoma in those patients with BRAF V600E mutation. This mutation is reported in about 50% of melanomas and is more common in melanomas on skin without chronic sun induced damage. The aim of this study was to evaluate the frequency of BRAF V600E mutation in Uruguayan melanoma patients, in order to analyze whether the use of vemurafenib would impact on our population. Methods: Formalin fixed, paraffin embedded tissues from 27 primary cutaneous melanomas, were obtained from files of the the Dermatopathology Unit, Department of Dermatology, Hospital de Clínicas in Montevideo, Uruguay. Most were Superficial Spreading Melanomas from skin without chronic sun induced damage. Microdissection of melanoma cells from paraffin embedded tissue was performed under microscopic visualization using a micromanipulator equipment. ADN extraction was performed and the BRAF V600E was detected by ASO-PCR. Results: Of the 27 melanoma samples analyzed, we detected the BRAF V600E mutation in 21. This determines a 77.8% frequency of mutation, a higher percentage than reported in the literature. This could be explained in different ways. The demographic characteristics of Uruguayan population are very peculiar, complying with a genetic admixture of Europeans(mostly from Spain), Amerindians (10%) and alow percentage of Africans (6%), which could explain the high incidence of BRAF V600E mutation. On the other hand, these melanomas were from skin without chronic sun induced damage, this type of melanomas have the highest rate of mutation. Finally, this mutation was analyzed in samples microdissected from melanoma biopsies, the fact that the cells were precisely removed from the tumor could also explain the high frequency of mutation. Conclusions: In this study we found a high frequency of BRAF V600E mutation in Uruguayan malignant melanoma patients, this could be explained by population genetic admixture, the melanoma subtype or technical characteristics. Further studies comparing techniques should be performed in our country to clarify this point.