Deregulated Genes in Sporadic Vestibular Schwannomas

Objective: In search of genes associated with vestibular schwannoma tumorigenesis, this study examines the gene expression in human vestibular nerve versus vestibular schwannoma tissue samples using microarray technology. Material and Methods: RNA was extracted from 3 vestibular nerves (serving as control) and 16 solid, sporadic vestibular schwannomas. RNA (5 mu g) was used in the labeling and biotinylation protocol to produce cRNA, which was hybridized to Affymetrix HG-U133A arrays. Data were imported into dChip v.1.3 and normalized using invariant set normalization. Differentially expressed genes were identified as differences between control and tumor tissue larger than 2-fold, with a conservative p value of less than 0.000001 and means of differences greater than 25. Results: Eighty-seven probe sets, representing 78 genes, were significantly up- or down-regulated in tumor tissue. The de-regulated genes were matched against established gene ontology, revealing that 8 of the up- regulated genes are involved in regulation of the cell cycle, 6 in cell morphogenesis, 8 in cell development, 11 in cell differentiation, 6 in cell death, 13 in cell adhesion, 9 in extracellular matrix, and 50 in protein binding (overlapping occurring). Gene annotation enrichment analyses of the clustered genes showed significant enrichment of annotations for the extracellular matrix (p < 0.0002), cell adhesion (p < 0.0001), and protein binding (p < 0.0004). Conclusion: We conclude that a number of transcripts are deregulated in sporadic vestibular schwannomas, and that several of these have functional annotations implicated in tumorigenesis. Specifically, genes involved in extracellular matrix function, cell adhesion, and protein binding seem to be of potential importance. However, further studies using other methodologies are needed for verification of the observed changes of gene expression seen by cDNA microarray analyses, for example, reverse-transcriptase-polymerase chain reaction and protein analyses.