Related Experiment Video
Updated: May 31, 2026
A Protocol for Explant Cultures of IDH1-mutant Diffuse Low-grade Gliomas
Published on: May 9, 2025
TET2 promoter methylation in low-grade diffuse gliomas lacking IDH1/2 mutations
Young-Ho Kim1, Daniela Pierscianek, Michel Mittelbronn
1International Agency for Research on Cancer, Lyon, France.
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.
