Pappas Center for Neuro-Oncology, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Cancer. 2017 Dec 1;123(23):4535-4546. doi: 10.1002/cncr.31039. Epub 2017 Oct 5.
The metabolic genes isocitrate dehydrogenase 1 (IDH1) and IDH2 are commonly mutated in low-grade glioma and in a subset of glioblastoma. These mutations co-occur with other recurrent molecular alterations, including 1p/19q codeletions and tumor suppressor protein 53 (TP53) and alpha thalassemia/mental retardation (ATRX) mutations, which together help to define a molecular signature that aids in the classification of gliomas and helps to better predict clinical behavior. A confluence of research suggests that glioma development in IDH-mutant and IDH wild-type tumors is driven by different oncogenic processes and responds differently to current treatment paradigms. Herein, the authors discuss the discovery of IDH mutations and associated molecular alterations in glioma, review clinical features common to patients with IDH-mutant glioma, and highlight current understanding of IDH mutation-driven gliomagenesis with implications for emerging treatment strategies. Cancer 2017;123:4535-4546. © 2017 American Cancer Society.
代谢基因异柠檬酸脱氢酶 1（IDH1）和 IDH2 在低级别胶质瘤和少部分胶质母细胞瘤中经常发生突变。这些突变与其他反复出现的分子改变共同发生，包括 1p/19q 缺失以及肿瘤抑制蛋白 53（TP53）和α地中海贫血/智力低下（ATRX）突变，这些改变共同有助于定义分子特征，有助于胶质瘤的分类，并有助于更好地预测临床行为。一系列研究表明，IDH 突变型和 IDH 野生型肿瘤的胶质瘤发生是由不同的致癌过程驱动的，并且对当前的治疗模式反应不同。本文作者讨论了 IDH 突变及其在胶质瘤中相关分子改变的发现，回顾了 IDH 突变型胶质瘤患者的常见临床特征，并强调了目前对 IDH 突变驱动的胶质瘤发生的理解，这对新兴的治疗策略具有重要意义。癌症 2017；123:4535-4546。©2017 美国癌症协会。
