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andreas von deimling 1p/19q codeleted oligodendroglioma month download article/chapter dependent isocitrate dehydrogenase christel herold-mende ruprecht-karls-universität heidelberg soluble isocitrate dehydrogenase full article pdf privacy choices/manage cookies tissue-dependent expression idh1 gene transcription andreas unterberg determine mutation types glioma-derived mutations human glioblastoma multiforme wolf mueller mitochondrial nad brain tumors heinrich-heine-university european economic area improving diagnostic accuracy radiation hybrid mapping central nervous system hepatic cells li-fraumeni syndrome parsons dw induce hif-1alpha skillful technical assistance preliminary data suggest article hartmann conditions privacy policy university hospital zurich expanding chemical biology kim yo accepting optional cookies arne christians integrated genomic analysis grant number 01es0729-30 common adult gliomas idh1 mutation clinical significance peroxisomal nadp author information authors idh1 r132c mutations mutation types main content log high-grade gliomas anaplastic glioma article log check access

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         headline:Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas
         description:Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas, oligodendrogliomas and oligoastrocytomas of WHO grades II and III. IDH2 encoding mitochondrial NADP+-dependent isocitrate dehydrogenase is also mutated in these tumors, albeit at much lower frequencies. Preliminary data suggest an importance of IDH1 mutation for prognosis showing that patients with anaplastic astrocytomas, oligodendrogliomas and oligoastrocytomas harboring IDH1 mutations seem to fare much better than patients without this mutation in their tumors. To determine mutation types and their frequencies, we examined 1,010 diffuse gliomas. We detected 716 IDH1 mutations and 31 IDH2 mutations. We found 165 IDH1 (72.7%) and 2 IDH2 mutations (0.9%) in 227 diffuse astrocytomas WHO grade II, 146 IDH1 (64.0%) and 2 IDH2 mutations (0.9%) in 228 anaplastic astrocytomas WHO grade III, 105 IDH1 (82.0%) and 6 IDH2 mutations (4.7%) in 128 oligodendrogliomas WHO grade II, 121 IDH1 (69.5%) and 9 IDH2 mutations (5.2%) in 174 anaplastic oligodendrogliomas WHO grade III, 62 IDH1 (81.6%) and 1 IDH2 mutations (1.3%) in 76 oligoastrocytomas WHO grade II and 117 IDH1 (66.1%) and 11 IDH2 mutations (6.2%) in 177 anaplastic oligoastrocytomas WHO grade III. We report on an inverse association of IDH1 and IDH2 mutations in these gliomas and a non-random distribution of the mutation types within the tumor entities. IDH1 mutations of the R132C type are strongly associated with astrocytoma, while IDH2 mutations predominantly occur in oligodendroglial tumors. In addition, patients with anaplastic glioma harboring IDH1 mutations were on average 6 years younger than those without these alterations.
         datePublished:2009-06-25T00:00:00Z
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      headline:Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: a study of 1,010 diffuse gliomas
      description:Somatic mutations in the IDH1 gene encoding cytosolic NADP+-dependent isocitrate dehydrogenase have been shown in the majority of astrocytomas, oligodendrogliomas and oligoastrocytomas of WHO grades II and III. IDH2 encoding mitochondrial NADP+-dependent isocitrate dehydrogenase is also mutated in these tumors, albeit at much lower frequencies. Preliminary data suggest an importance of IDH1 mutation for prognosis showing that patients with anaplastic astrocytomas, oligodendrogliomas and oligoastrocytomas harboring IDH1 mutations seem to fare much better than patients without this mutation in their tumors. To determine mutation types and their frequencies, we examined 1,010 diffuse gliomas. We detected 716 IDH1 mutations and 31 IDH2 mutations. We found 165 IDH1 (72.7%) and 2 IDH2 mutations (0.9%) in 227 diffuse astrocytomas WHO grade II, 146 IDH1 (64.0%) and 2 IDH2 mutations (0.9%) in 228 anaplastic astrocytomas WHO grade III, 105 IDH1 (82.0%) and 6 IDH2 mutations (4.7%) in 128 oligodendrogliomas WHO grade II, 121 IDH1 (69.5%) and 9 IDH2 mutations (5.2%) in 174 anaplastic oligodendrogliomas WHO grade III, 62 IDH1 (81.6%) and 1 IDH2 mutations (1.3%) in 76 oligoastrocytomas WHO grade II and 117 IDH1 (66.1%) and 11 IDH2 mutations (6.2%) in 177 anaplastic oligoastrocytomas WHO grade III. We report on an inverse association of IDH1 and IDH2 mutations in these gliomas and a non-random distribution of the mutation types within the tumor entities. IDH1 mutations of the R132C type are strongly associated with astrocytoma, while IDH2 mutations predominantly occur in oligodendroglial tumors. In addition, patients with anaplastic glioma harboring IDH1 mutations were on average 6 years younger than those without these alterations.
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            address:
               name:Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
      name:Arne Christians
      affiliation:
            name:German Cancer Research Center
            address:
               name:Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center, Heidelberg, Germany
               type:PostalAddress
            type:Organization
      name:Jörg Felsberg
      affiliation:
            name:Heinrich-Heine-University
            address:
               name:Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
               type:PostalAddress
            type:Organization
      name:Marietta Wolter
      affiliation:
            name:Heinrich-Heine-University
            address:
               name:Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
               type:PostalAddress
            type:Organization
      name:Christian Mawrin
      affiliation:
            name:Otto von Guericke Universität Magdeburg
            address:
               name:Department of Neuropathology, Otto von Guericke Universität Magdeburg, Magdeburg, Germany
               type:PostalAddress
            type:Organization
      name:Wolfgang Wick
      affiliation:
            name:Ruprecht-Karls-Universität Heidelberg
            address:
               name:Department of Neurooncology, Clinical Cooperation Unit Neurooncology DKFZ, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
      name:Michael Weller
      affiliation:
            name:University Hospital Zurich
            address:
               name:Department of Neurology, University Hospital Zurich, Zurich, Switzerland
               type:PostalAddress
            type:Organization
      name:Christel Herold-Mende
      affiliation:
            name:Ruprecht-Karls-Universität Heidelberg
            address:
               name:Department of Neurosurgery, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
      name:Andreas Unterberg
      affiliation:
            name:Ruprecht-Karls-Universität Heidelberg
            address:
               name:Department of Neurosurgery, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
      name:Judith W. M. Jeuken
      affiliation:
            name:Radboud University Nijmegen Medical Center
            address:
               name:Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
               type:PostalAddress
            type:Organization
      name:Peter Wesseling
      affiliation:
            name:Radboud University Nijmegen Medical Center
            address:
               name:Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
               type:PostalAddress
            type:Organization
      name:Guido Reifenberger
      affiliation:
            name:Heinrich-Heine-University
            address:
               name:Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
               type:PostalAddress
            type:Organization
      name:Andreas von Deimling
      affiliation:
            name:Ruprecht-Karls-Universität Heidelberg
            address:
               name:Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
               type:PostalAddress
            type:Organization
            name:German Cancer Research Center
            address:
               name:Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center, Heidelberg, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
      name:Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center, Heidelberg, Germany
      name:Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center, Heidelberg, Germany
      name:Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center, Heidelberg, Germany
      name:Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
      name:Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
      name:Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center, Heidelberg, Germany
      name:Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
      name:Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
      name:Department of Neuropathology, Otto von Guericke Universität Magdeburg, Magdeburg, Germany
      name:Department of Neurooncology, Clinical Cooperation Unit Neurooncology DKFZ, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
      name:Department of Neurology, University Hospital Zurich, Zurich, Switzerland
      name:Department of Neurosurgery, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
      name:Department of Neurosurgery, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
      name:Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
      name:Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
      name:Department of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany
      name:Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany
      name:Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center, Heidelberg, Germany
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