Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-50525

Weller, M; Wick, W; von Deimling, A (2011). Isocitrate dehydrogenase mutations: a challenge to traditional views on the genesis and malignant progression of gliomas. Glia, 59(8):1200-1204.

[img]Accepted Version
PDF - Registered users only
399kB

View at publisher

Abstract

Isocitrate dehydrogenases (IDHs) convert isocitrate to α-ketoglutarate by oxidative decarboxylation and are thereby involved in multiple metabolic processes. Mutations in the genes encoding IDH1 and IDH2 were first reported in human gliomas in 2008 and later on also identified in a minority of patients with acute myeloid leukemia. The mutations universally affect codons 132 in IDH1 and 172 in IDH2 and result in decreased enzymatic activity. The oncogenic pathway triggered by IDH mutations may involve the activation of hypoxia-inducible factor pathway as well as the acquisition of a novel (gain of enzymatic) function consuming NADPH and generating α-hydroxyglutarate. Most intriguingly, IDH mutations are observed in ∼70-80% of grade II/III gliomas and the majority of secondary glioblastomas, but only 10% of primary glioblastomas, suggesting a different cellular origin of the gliomas, which had previously been viewed as a multistep process of malignant progression. Understanding the oncogenic pathway mediated by mutant IDH might result in the development of novel, tailored pharmacological therapies for human glioma patients.

Citations

15 citations in Web of Science®
15 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

1 download since deposited on 04 Nov 2011
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
DDC:610 Medicine & health
Language:English
Date:2011
Deposited On:04 Nov 2011 12:26
Last Modified:24 Jan 2014 12:16
Publisher:Wiley-Blackwell
ISSN:0894-1491
Publisher DOI:10.1002/glia.21130
PubMed ID:21294161

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page