Expression of the BRAF L597Q mutation in sporadic neurofibromas of the upper extremity

Abstract

The pathogenesis of neurofibromas is poorly understood outside of neurofibromatosis (NF). The BRAF proto-oncogene has been implicated in malignant peripheral nerve sheath tumors (PNSTs), however its role in neurofibromas has not been described. In this study, we identify a BRAF mutation in a 61-year old non-NF patient with a history of sporadic and recurrent neurofibromas localized to the right upper extremity. Despite repeat resections to establish local control, he developed median nerve neuropathy secondary to a 13×4cm plexiform neurofibroma. Genetic sequencing of the neurofibroma revealed the expression of a novel BRAF L597Q mutation. This study is the first to describe the BRAF L597Q mutation in PNSTs and the first to implicate a BRAF mutation in neurofibroma biology. We hypothesize that BRAF mutations may identify a molecularly-distinct subset of recurrent neurofibromas and may provide potential for targeted therapeutics.