Analysis of CIC-associated CpG island methylation in oligoastrocytoma
Article first published online: 28 OCT 2013
© 2013 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 39, Issue 7, pages 831–836, December 2013
How to Cite
Sahm, F., Lass, U., Herold-Mende, C., von Deimling, A., Hartmann, C. and Mueller, W. (2013), Analysis of CIC-associated CpG island methylation in oligoastrocytoma. Neuropathology and Applied Neurobiology, 39: 831–836. doi: 10.1111/nan.12045
- Issue published online: 28 OCT 2013
- Article first published online: 28 OCT 2013
- Accepted manuscript online: 25 MAR 2013 04:40AM EST
- Manuscript Accepted: 15 MAR 2013
- Manuscript Received: 12 OCT 2012
- CpG island methylation;
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.
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.
Both methylation-specific PCR and subsequent bisulphite-sequencing of selected cases revealed an unmethylated status in all samples.
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.