研究人員發(fā)現(xiàn)了兩種控制惡性神經(jīng)膠質(zhì)瘤（malignant gliomas）生長(zhǎng)和發(fā)展的基因突變。惡性神經(jīng)膠質(zhì)瘤是一種很難治療的惡性腦部腫瘤,。
研究人員周三稱,，該發(fā)現(xiàn)為區(qū)分原發(fā)性多形性膠質(zhì)母細(xì)胞瘤和繼發(fā)性多形性膠質(zhì)母細(xì)胞瘤（primary and secondary glioblastoma multiforme）提供了可能,，研究還可能為新的治療途徑指明道路。美國(guó)參議員愛德華·肯尼迪（Edward Kennedy）就是患上了這種腦瘤,。
研究人員在《新英格蘭醫(yī)學(xué)雜志》(New England Journal of Medicine)上發(fā)表報(bào)告稱，該基因突變或許還能幫助預(yù)測(cè)哪位病人能活得更長(zhǎng),。
IDH1或IDH2基因發(fā)生突變的病人平均能活31個(gè)月,，相比之下,，腫瘤中這兩種基因都沒有發(fā)生突變的患者平均存活時(shí)間為15個(gè)月。
參與該項(xiàng)研究的杜克大學(xué)的閻海博士在聲明中說：“所有的多形性膠質(zhì)母細(xì)胞瘤基本都被認(rèn)為是一樣的,，并且也用同樣的方法治療。但我們的研究表明,，我們需要對(duì)它們區(qū)別對(duì)待。”
“試驗(yàn)結(jié)果很清楚,，六年來我一直在進(jìn)行腦部腫瘤的基因研究,，但我從未見過像這個(gè)研究那麼顯著的基因突變,。”（生物谷Bioon.com）
生物谷推薦原始出處：
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.
