PDF(Pubmed)
Abstract：
Neurofibromatosis type 2 (NF2), a multiple neoplasia syndrome, is a manifestation of an impaired expression of the merlin protein, exerting inhibitory effects on cell proliferation signals due to abnormalities of the NF2 gene located on chromosome 22. About half of patients inherit a germline mutation from a parent, and nearly 60% of de novo NF2 patients are estimated to have somatic mosaicism. The development of technical methods to detect NF2 gene mutation, including targeted deep sequencing from multiple tissues, improved the diagnostic rate of mosaic NF2. With improved understanding of genetics and pathogenesis, the diagnostic criteria for NF2 were updated to assist in identifying and diagnosing NF2 at an earlier stage. The understanding of cell signaling pathways interacting with merlin has led to the development of molecular-targeted therapies. Currently, several translational studies are searching for possible therapeutic agents targeting VEGF or VEGF receptors. Bevacizumab, an anti-VEGF monoclonal antibody, is widely used in many clinical trials aiming for hearing improvement or tumor volume control. Currently, a randomized, double-masked trial to assess bevacizumab is underway. In this randomized control trial, 12 other Japanese institutions joined the principal investigators in the clinical trial originating at Fukushima Medical University. In this review, we will be discussing the latest research developments regarding NF2 pathophysiology, including molecular biology, diagnosis, and novel therapeutics.
摘要：
2型神经纤维瘤病(NF2),多发性瘤形成综合征,是Merlin蛋白表达受损的表现，由于位于22号染色体上的NF2基因异常，对细胞增殖信号产生抑制作用。大约一半的患者从父母那里继承了种系突变，估计近60%的从头NF2患者有躯体镶嵌。NF2基因突变检测技术方法的发展,包括来自多个组织的靶向深度测序，提高了马赛克NF2的诊断率。随着对遗传学和发病机制的认识的提高，我们更新了NF2的诊断标准,以便在早期阶段协助识别和诊断NF2.对与merlin相互作用的细胞信号通路的理解导致了分子靶向治疗的发展。目前,一些翻译研究正在寻找可能的靶向VEGF或VEGF受体的治疗药物。贝伐单抗,抗VEGF单克隆抗体,广泛用于许多旨在改善听力或控制肿瘤体积的临床试验。目前,一个随机的，评估贝伐单抗的双盲试验正在进行中.在这项随机对照试验中，其他12个日本机构加入了福岛医科大学的临床试验的主要研究人员。在这次审查中,我们将讨论NF2病理生理学的最新研究进展，包括分子生物学，诊断,和新颖的疗法。
