研究人员发现了两种控制恶性神经胶质瘤（malignant gliomas）生长和发展的基因突变。恶性神经胶质瘤是一种很难治疗的恶性脑部肿瘤。
研究人员周三称，该发现为区分原发性多形性胶质母细胞瘤和继发性多形性胶质母细胞瘤（primary and secondary glioblastoma multiforme）提供了可能，研究还可能为新的治疗途径指明道路。美国参议员爱德华·肯尼迪（Edward Kennedy）就是患上了这种脑瘤。
研究人员在《新英格兰医学杂志》(New England Journal of Medicine)上发表报告称，该基因突变或许还能帮助预测哪位病人能活得更长。
IDH1或IDH2基因发生突变的病人平均能活31个月，相比之下，肿瘤中这两种基因都没有发生突变的患者平均存活时间为15个月。
参与该项研究的杜克大学的阎海博士在声明中说：“所有的多形性胶质母细胞瘤基本都被认为是一样的，并且也用同样的方法治疗。但我们的研究表明，我们需要对它们区别对待。”
“试验结果很清楚，六年来我一直在进行脑部肿瘤的基因研究，但我从未见过像这个研究那麽显着的基因突变。”（生物谷Bioon.com）
生物谷推荐原始出处：
NEJM Volume 360:765-773 February 19, 2009
IDH1 and IDH2 Mutations in Gliomas
Hai Yan, M.D., Ph.D., D. Williams Parsons, M.D., Ph.D., Genglin Jin, Ph.D., Roger McLendon, M.D., B. Ahmed Rasheed, Ph.D., Weishi Yuan, Ph.D., Ivan Kos, Ph.D., Ines Batinic-Haberle, Ph.D., Sian Jones, Ph.D., Gregory J. Riggins, M.D., Ph.D., Henry Friedman, M.D., Allan Friedman, M.D., David Reardon, M.D., James Herndon, Ph.D., Kenneth W. Kinzler, Ph.D., Victor E. Velculescu, M.D., Ph.D., Bert Vogelstein, M.D., and Darell D. Bigner, M.D., Ph.D.
ABSTRACT
Background A recent genomewide mutational analysis of glioblastomas (World Health Organization [WHO] grade IV glioma) revealed somatic mutations of the isocitrate dehydrogenase 1 gene (IDH1) in a fraction of such tumors, most frequently in tumors that were known to have evolved from lower-grade gliomas (secondary glioblastomas).
Methods We determined the sequence of the IDH1 gene and the related IDH2 gene in 445 central nervous system (CNS) tumors and 494 non-CNS tumors. The enzymatic activity of the proteins that were produced from normal and mutant IDH1 and IDH2 genes was determined in cultured glioma cells that were transfected with these genes.
Results We identified mutations that affected amino acid 132 of IDH1 in more than 70% of WHO grade II and III astrocytomas and oligodendrogliomas and in glioblastomas that developed from these lower-grade lesions. Tumors without mutations in IDH1 often had mutations affecting the analogous amino acid (R172) of the IDH2 gene. Tumors with IDH1 or IDH2 mutations had distinctive genetic and clinical characteristics, and patients with such tumors had a better outcome than those with wild-type IDH genes. Each of four tested IDH1 and IDH2 mutations reduced the enzymatic activity of the encoded protein.
Conclusions Mutations of NADP+-dependent isocitrate dehydrogenases encoded by IDH1 and IDH2 occur in a majority of several types of malignant gliomas.
