NFAT and T-Cell Response Play Major Roles in the Formation of Sporadic Vestibular Schwannomas

Introduction: Even though clinical and morphological differences of vestibular schwannomas are well documented, the knowledge on molecular mechanisms of development is limited. In this study, we examined differences in gene expression between tumor and control tissue in search of underlying disease-causing deregulated pathways.

Material and Methods: We performed whole genome microarray expression profiling (HG-U219 Array Plate, Affymetrix) and pathway analysis of tissue samples from 36 patients with sporadic vestibular schwannomas versus 7 postmortem samples of the vestibulocochlear nerve.

Results: We identified 2,694 genes that were deregulated over twofold: 1,471 were upregulated and 1,223 were downregulated. The most significantly deregulated pathways in vestibular schwannomas include the role of nuclear factor of activated T-cells (NFAT) in immune response, phospholipase C signaling and antigen presentation.

Conclusion: An important role in vestibular schwannoma formation is attributed to nuclear factors of activated T-cells and their transcriptional partners, whose combined interactions result in a deranged T-cell response and may thereby lead to an imbalance between tumorigenesis and immune response.