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Previous Volume 360:765-773 February 19, 2009 Number 8 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Thompson, C. B. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

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.

Source Information

From the Departments of Pathology (H.Y., G.J., R.M., B.A.R., D.D.B.), Radiation Oncology (I.K., I.B.-H.), Neuro-Oncology (H.F.), and Surgery (A.F., D.R.), the Pediatric Brain Tumor Foundation Institute and the Preston Robert Tisch Brain Tumor Center; and the Cancer Statistical Center (J.H.) — all at Duke University Medical Center, Durham, NC; the Ludwig Center for Cancer Genetics and Therapeutics and the Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center (D.W.P., S.J., K.W.K., V.E.V., B.V.) and the Department of Neurosurgery, Johns Hopkins Medical Institutions (G.J.R.) — all in Baltimore; the Department of Pediatrics, Baylor College of Medicine, Houston (D.W.P.); and the Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD (W.Y.).

Drs. Yan and Parsons contributed equally to this article.

Address reprint requests to Dr. Yan at the Department of Pathology, Pediatric Brain Tumor Foundation Institute and Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, or at yan00002{at}mc.duke.edu; or to Dr. Parsons at the Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, or at dwparson{at}txccc.org.

Full Text of this Article

Related Letters:

IDH1 and IDH2 Mutations in Gliomas
De Carli E., Wang X., Puget S., Ducray F., Marie Y., Sanson M., Reitman Z., Yan H.
Extract | Full Text | PDF  
N Engl J Med 2009; 360:2248-2249, May 21, 2009. Correspondence

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