Serial analysis of gene expression in neurofibromatosis type 2-associated vestibular schwannoma

The genesis, morphology, and growth characteristics of vestibular schwannomas are determined by genetic alterations which vary gene transcript expression and this transcript expression can be qualitatively and quantitatively evaluated using the SAGE technique. By use of such technique, gene products with tumorigenic potential may be identified, providing insight and targets for future study.

Serial analysis of gene expression (SAGE) is a powerful new technique that allows detailed qualitative and quantitative evaluation of cellular gene transcript expression. Tissue in limited quantity (5 x 10 to 2 x 10 cells) may be analyzed by a modified version of SAGE called microSAGE. Application of SAGE or microSAGE to study vestibular schwannoma gene expression has not been previously reported.

Fresh, vestibular schwannoma specimen from an individual with the diagnosis of neurofibromatosis type 2 was attained intraoperatively and maintained in a sealed container at -80degreesC until the time of analysis. The tissue was processed according to the microSAGE protocol, using 180 mg of vestibular schwannoma as starting material.

The protocol resulted in the generation and sequencing of a tag library involving 458 tags representing 277 different gene products, including many transcripts known to be expressed in vestibular schwannomas. Several gene products with tumorigenic potential were identified.

These data demonstrate that microSAGE is a useful technique to study vestibular schwannoma gene expression. Future studies will include building more comprehensive libraries and comparing libraries from various vestibular schwannoma phenotypes to identify useful diagnostic or prognostic markers, and targets for therapeutic intervention.