Article
IDH1 and IDH2 mutations and their role in progression of low grade and malignant gliomas
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Authors
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Tareq Juratli
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl-Gustav-Carus an der Technischen Universität Dresden, Deutschland
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Katja Robel
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl-Gustav-Carus an der Technischen Universität Dresden, Deutschland
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Gabriele Schackert
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl-Gustav-Carus an der Technischen Universität Dresden, Deutschland
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Dietmar Krex
- Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl-Gustav-Carus an der Technischen Universität Dresden, Deutschland
| Published: | September 16, 2010 |
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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 glioblastoma (sGBM) 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 malignant transformation of low grade astrocytomas (LGA) or with malignant progression of GBM.
Methods: The first study group comprised pGBM and their first recurrencies. The latter group was further divided into early recurrencies (between 30 and 180 days post primary resection) and late recurrencies (later than 300 days post primary resection). In the second population, patients with LGA and their concurrent recurrencies as sGBM were investigated. The genomic regions around IDH1 codon 132 and IDH2 codon 172 were PCR amplified and directly sequenced. The data was categorized according to clinical data (age, gender, etc.), tumor-related factors (location, histology, proliferation, etc.), and therapy related factors (adjuvant treatments, type of XRT, time to progression, survival).
Results: In the first cohort with 33 pGBM and their first recurrencies, only one mutation (1.5%) affecting codon 132 of IDH1 G395A (Arg132His) was detected in the recurrence of a late (390 d) pGBM. IDH2 mutation was not found in any of the pGBM nor its recurrencies. In the second group with 40 patients, sufficient material was available from 19 nonpilocytic low grade astrocytoma including 4 oligoastrocytoma WHO II° and from 36 sGBM. The IDH1 mutation was found in 11 LGA (58%) and 20 (55.5%) sGBM including 33 (97%) G395A and one (3%) G395C. Furthermore, three (5.45%) IDH2 mutations were identified in 1 LGA and 2 sGBM. In 7/15 (46.6%) of the cases the mutation was detected in the LGA as well as its malignant transformation to a sGBM and in 4 pts only the sGBM was affected The presence of IDH1 mutations correlated with a median PFS from 9 months vs. 11 months in the not-affected group. The median time to malignant progression was 33 months in the mutation group vs. 31 months in non-mutated group.
Conclusions: No association was found between the IDH1/IDH2 mutation and malignant transformation of LGA or further progression of pGBM or sGBM to early or late recurrencies.
