TET2 promoter methylation in low-grade diffuse gliomas lacking IDH1/2 mutations
- Young-Ho Kim1,
- Daniela Pierscianek1,
- Michel Mittelbronn2,
- Anne Vital3,
- Luigi Mariani4,5,
- Martin Hasselblatt6,
- Hiroko Ohgaki1
- 1International Agency for Research on Cancer, Lyon, France
- 2Department of Neuropathology, Neuroscience Center, Frankfurt, Frankfurt am Main, Germany
- 3Bordeaux Institute of Neuroscience, Bordeaux, France
- 4Department of Neurosurgery, University Hospital, Basel, Switzerland
- 5Department of Neurosurgery, University Hospital, Bern, Switzerland
- 6Institute of Neuropathology, University Hospital Munster, Munster, Germany
- Correspondence to Dr Hiroko Ohgaki, Section of Molecular Pathology, International Agency for Research on Cancer (IARC), 150 Cours Albert Thomas, Lyon 69372 Cedex 08, France; ohgaki{at}iarc.fr
- Accepted 26 May 2011
- Published Online First 20 June 2011
Abstract
Background Miscoding mutations of the TET2 gene, which encodes the α-ketoglutarate-dependent enzyme that catalyses the conversion of 5-methylcytosine to 5-hydroxymethylcytosine, thus producing DNA demethylation, have been detected in 10–25% of acute myeloid leukaemias lacking IDH1/2 mutations. Most low-grade diffuse gliomas carry IDH1/2 mutations (>85%), but molecular mechanisms of pathogenesis in those lacking IDH1/2 mutations remain to be elucidated.
Methods Miscoding mutations and promoter methylation of the TET2 gene were screened for in 29 low-grade diffuse gliomas lacking IDH1/2 mutations.
Results Single-strand conformational polymorphism followed by direct sequencing showed the absence of miscoding mutations in TET2. Methylation-specific PCR revealed methylation of the TET2 promoter in 5 of 35 cases (14%). In contrast, none of 38 low-grade diffuse gliomas with IDH1/2 mutations had TET2 promoter methylation (p=0.0216).
Conclusion Results suggest that TET2 promoter methylation, but not TET2 mutation, may be an alternative mechanism of pathogenesis in a small fraction of low-grade diffuse gliomas lacking IDH1/2 mutations.
- TET2
- IDH1
- IDH2
- glioma
- promoter methylation
- neuromuscular
- neuropathology
- neuro-oncology
- molecular oncology
- paediatric pathology
- brain tumourscancer research
- molecular pathology
Footnotes
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Funding DP is supported by the Fritz-Thyssen Foundation.
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Competing interests None.
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Ethics approval Ethics approval was provided by IARC.
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Provenance and peer review Not commissioned; externally peer reviewed.
