Artikel
The formation of sporadic vestibular schwannomas: microarray gene expression analysis reveals the role of NFAT and T-cell response
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Veröffentlicht: | 4. Juni 2012 |
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Gliederung
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Objective: Even though clinical and morphological differences of vestibular schwannomas are well documented, the knowledge on molecular mechanisms of development is sparse. In this study, we examined differences in gene expression between tumor and control tissue in search of underlying disease-causing deregulated pathways.
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 seven postmortem samples of the vestibulocochlear nerve. Network-based pathway analysis (Ingenuity Pathway Analysis) was used to determine the most significantly associated pathways.
Results: 2,694 genes that were deregulated over 2 fold were identified: 1,471 were up- and 1,223 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.
Conclusions: 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.