RT Journal Article
SR Electronic
T1 <em>TET2</em> promoter methylation in low-grade diffuse gliomas lacking <em>IDH1/2</em> mutations
JF Journal of Clinical Pathology
JO J Clin Pathol
FD BMJ Publishing Group Ltd and Association of Clinical Pathologists
SP 850
OP 852
DO 10.1136/jclinpath-2011-200133
VO 64
IS 10
A1 Young-Ho Kim
A1 Daniela Pierscianek
A1 Michel Mittelbronn
A1 Anne Vital
A1 Luigi Mariani
A1 Martin Hasselblatt
A1 Hiroko Ohgaki
YR 2011
UL http://jcp.bmj.com/content/64/10/850.abstract
AB 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 (&gt;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.