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Updated: May 13, 2026
Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 (Kir4.1)
Published on: September 26, 2015
Analysis of CIC-associated CpG island methylation in oligoastrocytoma
F Sahm1, U Lass, C Herold-Mende
1Department of Neuropathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Aims:
Combined deletion of the whole chromosomal arms 1p and 19q is a frequent event in oligodendroglial tumours. Recent identification of recurrent mutations in CIC on 19q and FUBP1 on 1p and their mutational patterns suggest a loss of function of the respective proteins. Surprisingly, oligoastrocytomas harbouring identical genetic characteristics regarding 1p/19q codeletion and frequent IDH1/2 mutations have been shown to carry CIC mutations in a significantly lower number of cases. The present study investigates whether epigenetic modification may result in silencing of CIC.
Methods:
As IDH1/2 mutation-mediated DNA hypermethylation is a prominent feature of these tumours, we analysed a set of CIC wild-type oligoastrocytomas and other diffuse gliomas with regard to 1p/19q status for presence of CIC-associated CpG island methylation by methylation-specific PCR.
Results:
Both methylation-specific PCR and subsequent bisulphite-sequencing of selected cases revealed an unmethylated status in all samples.
Conclusion:
Despite the hypermethylator phenotype in IDH1/2 mutant tumours and recent detection of gene silencing particularly on retained alleles in oligodendroglial tumours, hypermethylation of CIC-associated CpG islands does not provide an alternative mechanism of functional CIC protein abrogation.
Insights
Epigenetic analysis of CIC-associated CpG islands in gliomas revealed no methylation. This indicates that hypermethylation does not cause functional CIC protein loss in these tumors, even with IDH1/2 mutations.
Area of Science:
- Neuro-oncology
- Cancer epigenetics
- Molecular pathology
Background:
- Combined 1p and 19q chromosomal arm deletion is common in oligodendroglial tumors.
- Mutations in CIC and FUBP1 suggest loss of function, but CIC mutations are less frequent in oligoastrocytomas with 1p/19q codeletion and IDH1/2 mutations.
- Investigating epigenetic silencing of CIC is crucial given the hypermethylator phenotype in IDH1/2 mutant gliomas.
Purpose of the Study:
- To investigate whether epigenetic modification, specifically CpG island methylation, leads to CIC gene silencing in gliomas.
- To determine if CIC methylation explains the lower frequency of CIC mutations in oligoastrocytomas with 1p/19q codeletion and IDH1/2 mutations.
Main Methods:
- Analysis of CIC wild-type oligoastrocytomas and other diffuse gliomas with known 1p/19q status.
- Methylation-specific PCR to detect CIC-associated CpG island methylation.
- Bisulphite-sequencing of selected cases for confirmation.
Main Results:
- Methylation-specific PCR and bisulphite-sequencing showed no methylation in the analyzed CIC-associated CpG islands.
- All tested glioma samples exhibited an unmethylated status at the CIC locus.
Conclusions:
- Hypermethylation of CIC-associated CpG islands is not an alternative mechanism for functional CIC protein loss in gliomas.
- This finding excludes epigenetic silencing via hypermethylation as an explanation for the observed CIC mutation patterns in specific glioma subtypes.
