摘要
胶质瘤是颅内最常见的恶性肿瘤,发病率逐年增高。越来越多的证据表明IDH1基因突变与胶质瘤密切相关。本文就近年来有关胶质瘤与IDH1基因突变的研究作一综述。IDH1基因编码胞浆内NADP依赖的异柠檬酸脱氢酶,后者能够对异柠檬酸进行催化生成α-酮戊二酸。在40%的胶质瘤中存在IDH1突变,在继发性胶质母细胞瘤中变异率最高。作为一种代谢的关键酶,IDH1突变后可以将α-KG转变成2-HG,后者具有促进细胞增殖和促进肿瘤发生的作用。而且,IDH1突变可以导致胶质瘤代谢和表观遗传学方面的改变。同时,IDH1突变可以通过增加HIF-1α水平及活性增加血管生成。目前在不同级别的胶质瘤当中,IDH1突变已经成为一个与预后密切相关的独立预测因素。对IDH1突变的研究有助于深入了解胶质瘤病因及干预措施的具体机制,有助于胶质瘤的分子水平分类和治疗。
Glioma is the most common malignant intraeranial tumor,with the increase of prevalence. Mounting evidences suggest the correlatin between IDH1 gene mutation and glioma. This article reviews the research on glioma and IDH1 gene mutation. 1DH1 encodes the cytoplasmic NADP dependent isocitrate dehydrogenase 1 that catalyzes the oxidative decarboxylation of isocitrate into α-ketoglutarate. IDH1 is mutated in 40 % of gliomas, with most common in secondary glioblastoma. As an important metabolic enzyme, IDH1 mutation results in a new enzymatic activity transforming α-ketoglutarate into 2-hydroxyglutarate （2-HG）. The oncometabolite 2-HG accumulates in the cell and acts as a competitive inhibitor of many α-ketoglutaratment of novel molecular classification and therapy.e dependent cellular reactions. Moreover, IDH1 mutation may alter the metabolism and epigenome of gliomas. Furthermore, IDH1 mutation increased angiogenesis because of accumulation of HIF-1α. IDH1 mutation is a strong and independent predictor of survival, whatever grade considered. Studies of IDH1 mutations have provided mechanistic insights into tumorigenesis and potential avenues for therapeutic intervention, and may lead to the development of novel molecular classification and therapy.
出处
《现代生物医学进展》
CAS
2015年第13期2554-2557,共4页
Progress in Modern Biomedicine
基金
黑龙江省科学技术厅攻关项目(GC08C413
GC12C303-1)
