Division of Neurosurgery, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada2Faculty of Medicine, University of St Andrews, St Andrews, Scotland.
Department of Laboratory Medicine and Pathobiology, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada4Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, Canada.
JAMA Neurol. 2014 Oct;71(10):1319-25. doi: 10.1001/jamaneurol.2014.1205.
Over the past 4 years, our understanding of gliomagenesis and the practice of neuro-oncology have been radically changed by the discovery of mutations involving the isocitrate dehydrogenase (IDH) enzymes. IDH mutation has been found to be an inciting event in gliomagenesis and to have a profound effect on the molecular and genetic route of oncogenic progression and on clinical outcome.
To review the role of IDH enzymes in normal physiology and describe aberrations in the IDH pathway that are associated with gliomagenesis, to review recent work examining the effect of IDH-targeted therapy in cancers harboring IDH mutation, and to determine how this work has expanded our understanding of the role of IDH in the development and progression of glioma.
A systematic review of the literature dating from 2008, when IDH mutation was discovered to be clinically significant in glioma, to 2013 was performed using the PubMed database. The following search terms were used: IDH, IDH1, IDH2, and isocitrate dehydrogenase, in conjunction with glioma or leukemia. The search was limited to articles published in English. Further hand searching was performed using a review of the pertinent references from the identified publications. All identified original articles were investigated for content and critiqued by Z.T. and S.D.
IDH mutation is an early event in gliomagenesis and has significant implications for glioma progression and tumor behavior. Early evidence suggests that IDH may be a therapeutic target in IDH-mutant gliomas.
IDH mutation is a central and defining event in the development and progression of glioma and may be a key target for future therapies for these types of neoplasms.
在过去的 4 年中，通过发现涉及异柠檬酸脱氢酶（IDH）酶的突变，我们对神经胶质瘤发生和神经肿瘤学实践的认识发生了根本变化。IDH 突变已被发现是神经胶质瘤发生的启动事件，并对致癌进展的分子和遗传途径以及临床结果产生深远影响。
回顾 IDH 酶在正常生理中的作用，并描述与神经胶质瘤发生相关的 IDH 途径异常，回顾最近研究 IDH 靶向治疗在携带 IDH 突变的癌症中的作用，并确定这些工作如何扩展了我们对 IDH 在胶质瘤发生和进展中的作用的理解。
使用 PubMed 数据库对 2008 年（当 IDH 突变被发现对胶质瘤具有临床意义时）至 2013 年的文献进行了系统回顾。使用了以下搜索词：IDH、IDH1、IDH2 和异柠檬酸脱氢酶，与胶质瘤或白血病一起使用。搜索仅限于以英语发表的文章。通过对已确定出版物的相关参考文献的审查，进一步进行了手工搜索。对所有确定的原始文章进行了内容调查，并由 Z.T. 和 S.D.进行了批评。
IDH 突变是神经胶质瘤发生的早期事件，对神经胶质瘤的进展和肿瘤行为有重大影响。早期证据表明，IDH 可能是 IDH 突变型神经胶质瘤的治疗靶点。
IDH 突变是胶质瘤发生和进展的核心和决定性事件，可能是这些类型肿瘤未来治疗的关键靶点。
