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Published on: January 14, 2014
IDH1 and IDH2 mutations in gliomas
Hai Yan1, D Williams Parsons, Genglin Jin
1Department of Pathology, Pediatric Brain Tumor Foundation Institute, Duke University Medical Center, Durham, NC 27710, USA. yan00002@mc.duke.edu
The New England Journal of Medicine
|February 21, 2009
Summary
Mutations in isocitrate dehydrogenase genes (IDH1 and IDH2) are common in malignant gliomas, particularly those evolving from lower-grade tumors. These IDH mutations are linked to distinct tumor characteristics and improved patient outcomes.
Area of Science:
- Neuro-oncology
- Cancer Genomics
- Molecular Biology
Background:
- Glioblastomas (WHO grade IV glioma) can arise from lower-grade gliomas.
- Genomewide analysis revealed isocitrate dehydrogenase 1 (IDH1) mutations in a subset of glioblastomas, especially secondary glioblastomas.
Purpose of the Study:
- To investigate the frequency and spectrum of IDH1 and IDH2 mutations in central nervous system (CNS) tumors.
- To assess the functional impact of IDH1 and IDH2 mutations on enzymatic activity.
- To correlate IDH mutations with tumor genetics, clinical features, and patient outcomes.
Main Methods:
- Sequencing of IDH1 and IDH2 genes in 445 CNS tumors and 494 non-CNS tumors.
- Assessing enzymatic activity of wild-type and mutant IDH1/IDH2 proteins in transfected glioma cells.
Main Results:
- IDH1 mutations (at amino acid 132) found in over 70% of WHO grade II/III astrocytomas/oligodendrogliomas and secondary glioblastomas.
- IDH2 mutations (at amino acid R172) identified in IDH1 wild-type tumors.
- IDH1/IDH2 mutated tumors exhibited unique genetic/clinical profiles and were associated with better patient prognosis.
- Tested IDH1 and IDH2 mutations demonstrably reduced protein enzymatic activity.
Conclusions:
- Mutations in NADP(+)-dependent isocitrate dehydrogenases (IDH1 and IDH2) are prevalent in various malignant gliomas.
- IDH1 and IDH2 mutations represent a significant molecular event in glioma development and progression.
- The presence of IDH mutations serves as a potential biomarker for improved outcomes in glioma patients.
