CpG island hypermethylation of the neurofibromatosis type 2 (NF2) gene is rare in sporadic vestibular schwannomas.
OBJECTIVE
Loss of both wild-type copies of the neurofibromatosis type 2 (NF2) gene is found in both sporadic and neurofibromatosis type 2-associated vestibular schwannomas (VS). Previous studies have identified a subset of VS with no loss or mutation of NF2. We hypothesized that methylation of NF2 resulting in gene silencing may play a role in such tumours.


METHODS
Forty sporadic VS were analysed by array comparative genomic hybridization using 1 Mb whole genome and chromosome 22 tile path arrays. The NF2 genes were sequenced and methylation of NF2 examined by pyrosequencing.


RESULTS
Monosomy 22 was the only recurrent change found. Twelve tumours had NF2 mutations. Eight tumours had complete loss of wild-type NF2, four had one mutated and one wild-type allele, 11 had only one wild-type allele and 17 showed no abnormalities. Methylation analysis showed low-level methylation in four tumours at a limited number of CpGs. No high-level methylation was found.


CONCLUSIONS
This study shows that a significant proportion of sporadic VS (>40%) have unmethylated wild-type NF2 genes. This indicates that other mechanisms, yet to be identified, are operative in the oncogenesis of these VSs.
Kullar
P J
PJ
Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Pearson
D M
DM
Malley
D S
DS
Collins
V P
VP
Ichimura
K
K
D000328:Adult; D000368:Aged; D055028:Comparative Genomic Hybridization; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D016515:Genes, Neurofibromatosis 2; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009464:Neuroma, Acoustic / Q000235:genetics*