Artikel
Microarray based comparison of Neurofibromatosis Type 2 associated vestibular schwannomas show an over-expression of TSPAN8 compared to the sporadic form
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Veröffentlicht: | 28. April 2011 |
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Objective: Vestibular schwannomas, also known as acoustic neuromas, are benign tumors of the vestibular part of the eighth cranial nerve, the vestibulocochlear nerve. 95% of the cases are sporadic, non-familiar and unilateral. In 5% of the cases they are bilateral and caused by the autosomal dominant disease neurofibromatosis type 2 (NF2). The NF2 associated vestibular schwannomas and the more common sporadic unilateral vestibular schwannomas both have biallelic mutations on the NF2 gene, which is localized on chromosome 22q12. We sought to determine the difference in gene expression between the NF2 associated form vs. the sporadic form.
Methods: We compared microarray-based gene expression of 36 samples of sporadic vestibular schwannomas with 13 NF 2 associated cases. Per array 100 ng of total RNA were amplified (3‘ IVT Express Kit, Affymetrix), marked and hybridized onto a gene chip containing more than 36.000 transcripts (HG-U219, Affymetrix). On the basis of the Lowess-normalized ratios, analytical tools in GeneSpring GX were systematically employed to extract differentially expressed genes between the NF2 associated and sporadic cases.
Results: Analysis of NF2 and sporadic cases revealed 285 differentially expressed genes (62 over-expressed and 223 under-expressed). The most significantly over-expressed gene in the NF2 associated tumor samples was TSPAN8 (tetraspanin 8) (2.94 log2fold, p = 7.8 x 10-9).
Conclusions: TSPAN 8 is a prometagenic and proangiogenetic factor, which is over-expressed in gastrointestinal tumors. It has been described to be involved in tumor progression and metastasis. In NF2 associated tumors tetraspanin 8 may play a role in the manifestation of the bilateral form of vestibular schwannomas as compared to the sporadic (unilateral) form.