Analysis of CIC-associated CpG island methylation in oligoastrocytoma

• Verfasst von: Sahm, Felix [VerfasserIn]
• Verfasst von: Lass, U. [VerfasserIn]
• Verfasst von: Herold-Mende, Christel [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Verfasst von: Hartmann, Christian [VerfasserIn]
• Verfasst von: Müller, Wolf C. [VerfasserIn]
• Titel: Analysis of CIC-associated CpG island methylation in oligoastrocytoma
• Verf.angabe: F. Sahm, U. Lass, C. Herold-Mende, A. von Deimling, C. Hartmann, W. Mueller
• E-Jahr: 2013
• Jahr: 25 March 2013
• Umfang: 6 S.
• Fussnoten: Gesehen am 25.01.2022
• Titel Quelle: Enthalten in: Neuropathology & applied neurobiology
• Ort Quelle: Oxford [u.a.] : Wiley-Blackwell, 1975
• Jahr Quelle: 2013
• Band/Heft Quelle: 39(2013), 7 vom: Dez., Seite 831-836
• ISSN Quelle: 1365-2990
• DOI: doi:10.1111/nan.12045
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: 1p/19q
• Sach-SW: CIC
• Sach-SW: CpG island methylation
• Sach-SW: gCIMP
• Sach-SW: IDH1
• Sach-SW: oligoastrocytoma
• K10plus-PPN: 1787057844

Abstract

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.