Controversies in Intrapatient Melanoma BRAFV600E Mutation Status

Therapies targeting the BRAF(V600) oncogene have improved the overall and disease-free survival of patients with advanced melanomas. An unresolved issue in clinical practice is the existence (or not) of BRAF(V600)-mutated and BRAF(V600)-nonmutated tumors in individual patients (intrapatient BRAF mutation heterogeneity), which may serve as a mechanism of resistance to BRAF inhibitors or lead to diagnostic problems. Different research groups have reported differing results after analyzing the BRAF mutation statuses of multiple melanoma tumors. Herein, we present a brief revision of the literature on this controversial topic and propose a theory to justify the divergence of the results found in the literature.