Lack of neurofibromatosis type 2 gene promoter methylation in sporadic vestibular schwannomas.

BACKGROUND

Vestibular schwannomas (VS) are benign tumors of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). In VS, losses of chromosomal material and mutations of the NF2 gene have been established to be causative. For a subset of VS without detectable gene alterations, promoter inactivation by hypermethylation has been suggested. However, published data are very limited and contradictory.

METHODS

We analyzed NF2 gene promoter methylation in 35 sporadic VS by methylation-specific PCR.

RESULTS

Twenty-three of the tumors were informative, showing no promoter methylation. In the remaining 12 tumors, promoter methylation could neither be verified nor excluded.

CONCLUSIONS

Our study suggests that NF2 gene inactivation by promoter hypermethylation is a rare or very uncommon mechanism of NF2 gene inactivation in sporadic VS. Other mechanisms destabilizing the NF2 gene product, yet to be identified, might play a role in the genesis of VS apart from the loss or mutation of the NF2 gene.