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IDH1 IDH2 Mutations Linked to Malignant Glioma

Gliomas with isocitrate dehydrogenase mutations were distinct from gliomas with wild-type genes

WEDNESDAY, Feb. 18 (HealthDay News) -- Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 appear to play a role in the pathogenesis of malignant gliomas, according to research published in the Feb. 19 issue of the New England Journal of Medicine.

Hai Yan, M.D., Ph.D., of the Duke University Medical Center in Durham, N.C., and colleagues analyzed data from 445 central nervous system tumors and 494 tumors from a variety of other locations. The investigators assessed the IDH1 and IDH2 sequences from the tumors.

More than 70 percent of grade II and III astrocytomas and oligodendrogliomas, as well as glioblastomas that developed from these, had mutations affecting amino acid 132 of IDH1, the researchers report. No samples of non-central nervous system tumors showed R132 mutations. Mutations in IDH1 or IDH2 were not found in any grade I pilocytic astrocytomas. The investigators tested four IDH1 and IDH2 mutations in an oligodendroglioma line, and in each, the IDH proteins' enzymatic activity was eliminated.

Findings from this study suggest "that mutations in IDH1 play a unique role in the pathogenesis of gliomas. If it turns out that the mutations result in the activation of IDH1 under physiologic conditions, then this work will have identified a potential molecular target for the treatment of cancers of the central nervous system," writes Craig B. Thompson, M.D., of the University of Pennsylvania in Philadelphia, in an accompanying editorial.

The study was supported by funding from Beckman Coulter, and several co-authors are eligible for royalties from products related to research discussed in the article.

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