gms | German Medical Science

62nd Annual Meeting of the German Society of Neurosurgery (DGNC)
Joint Meeting with the Polish Society of Neurosurgeons (PNCH)

German Society of Neurosurgery (DGNC)

7 - 11 May 2011, Hamburg

IDH mutations and their role in the progression of low grade gliomas

Meeting Abstract

  • T. Juratli - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl-Gustav-Carus der Technischen Universität Dresden
  • K. Robel - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl-Gustav-Carus der Technischen Universität Dresden
  • G. Schackert - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl-Gustav-Carus der Technischen Universität Dresden
  • D. Krex - Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl-Gustav-Carus der Technischen Universität Dresden

Deutsche Gesellschaft für Neurochirurgie. Polnische Gesellschaft für Neurochirurgen. 62. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgen (PNCH). Hamburg, 07.-11.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. DocMI.05.02

DOI: 10.3205/11dgnc211, URN: urn:nbn:de:0183-11dgnc2119

Published: April 28, 2011

© 2011 Juratli et al.
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Outline

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Objective: Somatic mutations in the gene encoding isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are frequently found in secondary malignant gliomas and are of prognostic value. In primary glioblastoma (pGBM), IDH1 and IDH2 mutations are rare. It is yet unclear whether IDH1 and/or IDH2 mutations are associated with recurrences of low grade gliomas (LGG) or with their malignant transformation.

Methods: In our population, patients with LGG and their concurrent recurrencies as malignant gliomas were investigated. The genomic regions around IDH1 codon 132 and IDH2 codon 172 were PCR amplified and directly sequenced. The data were categorized according to clinical data (age, gender, etc.), tumor-related factors (location, histology, proliferation, MGMT promoter methylation), and therapy related factors (adjuvant treatments, type of XRT, time to progression, survival).

Results: The entire population consisted of 67 patients. Sufficient material was available from 30 nonpilocytic low grade gliomas including 6 oligoastrocytomas WHO II° and from 67 malignant gliomas (24 anaplastic astrocytoma and 43 secondary glioblastomas). The IDH1 mutation was found in 20/30 LGG (66.6%) and in 49/67 (73.1%) malignant gliomas. In 20/30 (66.6%) of the cases, the mutation was detected in the LGG as well as its malignant transformation to a malignant glioma. The presence of IDH1 mutation in the LGG correlated with a significantly longer progression-free (80.9) and overall survival (OS) (122.3) compared to the wildtype group (39.6 vs. 46 months, respectively). After progression to a malignant glioma, the median OS in the IDH1 mutated group was also superior (105.7 vs. 73.8 months). IDH1 mutations were found to be prognostically important in the radiotherapy- and the radiotherapy/chemotherapy-treated patients, for OS, but not for the progression-free survival independently of the adjuvant therapy after malignant transformation. Furthermore, IDH1 mutations were strongly associated with MGMT promoter methylation.

Conclusions: In this group of patients with low grade gliomas and their progression to malignant gliomas, the presence of IDH1 mutations was found to carry a very strong prognostic significance for OS without evidence of a predictive significance for longer progression-free survival after malignant transformation.