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Isocitrate Dehydrogenase (IDH) Mutation in Gliomas

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Next Generation Sequencing in Cancer Research, Volume 2

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Abstract

First identified in 2006 in a colorectal cancer sequencing effort, Isocitrate Dehydrogenase (IDH) mutations were later reported in secondary glioblastomas by Parsons et al. leading the way for further studies which have revealed the presence of mutations in either IDH1 or IDH2 in over 70 % of grade II–III gliomas and secondary glioblastomas. In the clinic, IDH1 and IDH2 mutations are important prognostic factors associated with prolonged survival and enhanced radio- and chemo-sensitivity. At the benchside, IDH mutations are a major focus of glioma research. Significant progresses have been made elucidating the roles of IDH mutations in tumorigenesis. IDH mutations were shown to confer a neomorphic enzymatic activity: the reduction of α-Ketoglutarate (αKG) to 2-hydroxyglutarate (2HG). 2HG was further shown to be the main mediator of the oncogenic effects of IDH mutation leading to epigenetic alterations, extracellular matrix remodeling, and hypoxia-inducible factor 1α (HIF1a) degradation. However, many aspects remain unclear such as the potential influence of IDH mutations on cancer cell metabolism and whether IDH mutations, despite increasingly well-characterized oncogenic mechanisms, may also trigger pro-survival effects. Elucidating the roles of mutant IDH enzymes in tumorigenesis will significantly improve our understanding of glioma biology and will lead to novel therapeutic strategies that should aim to disrupt the oncogenic properties of IDH mutations while promoting properties that may contribute to the slower growth, enhanced sensitivity to conventional therapies and overall longer survival characteristic of IDH mutant gliomas.

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  1. South Alberta Cancer Research Institute (SACRI), Cumming Medical School, University of Calgary, Calgary, AB, Canada

    Charles Chesnelong

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  1. Department of Pathology and Laboratory, Medicine, Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada

    Wei Wu

  2. Faculty of Science, Biochemistry Department, Center of Innovation in Personalized Medicine, King Fahd Center for Medical Research, King Abdulaziz University, Jeddah, Saudi Arabia

    Hani Choudhry

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Chesnelong, C. (2015). Isocitrate Dehydrogenase (IDH) Mutation in Gliomas. In: Wu, W., Choudhry, H. (eds) Next Generation Sequencing in Cancer Research, Volume 2. Springer, Cham. https://doi.org/10.1007/978-3-319-15811-2_25

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