title: Analysis of CIC-associated CpG island methylation in oligoastrocytoma.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuropathology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Neuropathology G380, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Sahm
authors.forename: U
authors.initials: U
authors.lastname: Lass
authors.forename: C
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: A
authors.initials: A
authors.lastname: von Deimling
authors.forename: C
authors.initials: C
authors.lastname: Hartmann
authors.forename: W
authors.initials: W
authors.lastname: Mueller
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009837:Oligodendroglioma / Q000235:genetics*
keywords: 1p/19q; CIC; CpG island methylation; IDH1; gCIMP; oligoastrocytoma