Letter to the Editor - The BRAF V600E Mutation is Not Present in All Cells of the Primary Melanoma and May Not Be Detected in All Metastatic Sites

Lars Alexander Schneider,Thomas Menzel,Dietmar Thal,Peter Moller,Karin Scharffetter-Kochanek,Thomas F.E Barth,Margit Anna Huber,Ralf Marienfeld

doi:10.2174/1874372201307010008

Abstract

The invention of targeted therapy for advanced stage melanoma has made it necessary to perform a mutation analysis of each melanoma case in order to detect the BRAF V600E mutation required for the prescription of selective BRAF inhibitors. In this new clinical context it is important to realize that the tumour seeds may come from different tumour clones and thus not all carry the mutation. We present an illustrative case that shows this phenomenon and discuss the consequences for clinical management in case of possible false negative mutation testing.

Highlights

DEAR EDITOR, Recognition of the genetic profile of the BRAF V600E driver mutation [1,2,3] in malignant melanoma has led to the development of inhibitors blocking mutated BRAF [2, 4, 5]
One of our patients taught us that melanoma metastases are clonal evolutions and, BRAF V600E analysis should be performed from different sites, if a wildtype status is detected in one probe
We proceeded and analysed microdissected material from the primary tumour from 2005; we found the BRAF V600E mutation in about 40% of the analysed BRAF alleles

Summary

Introduction

DEAR EDITOR, Recognition of the genetic profile of the BRAF V600E driver mutation [1,2,3] in malignant melanoma has led to the development of inhibitors blocking mutated BRAF [2, 4, 5]. Genetic studies estimate that about 50% of these patients carry a V600E BRAF mutation [6]. In the first instance there is a need for a mutational analysis of excised tumour tissue prior to starting therapy since only patients with the BRAFV600E mutation benefit from this targeted therapy.

Results

Conclusion