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J Clin Pathol 64:850-852 doi:10.1136/jclinpath-2011-200133
  • Original article

TET2 promoter methylation in low-grade diffuse gliomas lacking IDH1/2 mutations

Editor's Choice
  1. Hiroko Ohgaki1
  1. 1International Agency for Research on Cancer, Lyon, France
  2. 2Department of Neuropathology, Neuroscience Center, Frankfurt, Frankfurt am Main, Germany
  3. 3Bordeaux Institute of Neuroscience, Bordeaux, France
  4. 4Department of Neurosurgery, University Hospital, Basel, Switzerland
  5. 5Department of Neurosurgery, University Hospital, Bern, Switzerland
  6. 6Institute of Neuropathology, University Hospital Munster, Munster, Germany
  1. 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.

Footnotes

  • Funding DP is supported by the Fritz-Thyssen Foundation.

  • Competing interests None.

  • Ethics approval Ethics approval was provided by IARC.

  • Provenance and peer review Not commissioned; externally peer reviewed.