神経線維腫症2型—Precision medicineの最新情報

Current Topics on Precision Medicine for Neurofibromatosis Type 2

Point

・神経線維腫症2型は，腫瘍抑制遺伝子であるNF2の異常によりmerlin蛋白の発現が障害された結果発症する．

・半数以上は体細胞モザイクによる孤発例と考えられ，複数組織のディープシークエンスにより診断能が向上することが期待される．

・現在，VEGFに対する分子標的薬であるベバシズマブや，VEGF受容体に対するペプチドワクチンを用いた臨床試験が行われている．

　Neurofibromatosis type 2（NF2）is a hereditary condition that causes bilateral vestibular schwannomas（VS）, multiple schwannomas, and meningiomas. The prognosis is poor because the multiplicity of the tumors leads to a progressive decline in the quality of life, deafness, and death in an early age. NF2 is caused by a disorder in the tumor suppressor gene NF2, which encodes the merlin protein. Although it is an autosomal dominant disease, more than half of cases are presumed to be de novo caused by somatic mosaicism, the diagnosis rate of which has been improved by the recently introduced technology of targeted deep sequencing of DNA from multiple tissues. No chemotherapeutic drugs for treating NF2-related VS are available at present, and surgery and radiotherapy remain the only therapeutic options. Recently, a randomized, double-blind, multicenter clinical trial has started in Japan to verify the efficacy and safety of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, in treating NF2-related VS.