Artikel
Expression of SWI/SNF-subunit BAF170 (BRG1-associated factor 170) in peripheral and vestibular schwannomas
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Veröffentlicht: | 11. September 2012 |
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Gliederung
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Until now several studies demonstrated mutations of the SWI/SNF protein SMARCB1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (INI1 (integrase interactor 1)) in malignant tumors such as in rhabdoid tumours, AT/RTs (atypical teratoid/rhabdoid tumors), and in sarcomas as well as in benign tumors like meningiomas and schwannomas, the latter being associated with schwannomatosis. The SWI/SNF (SWItch/Sucrose NonFermen-table) complex consists of nine essential and variable subunits, including an ATPase subunit being necessary for chromatin remodelling which makes compacted DNA accessible for transcription factors and RNA polymerases. This evolutionary highly conserved complex regulates essential processes such as DNA methylation, reparation, recombination and replication.
In order to identify other SWI/SNF subunits beside INI1 which may be involved in the development of schwannomas, we determined expression patterns of BRG1, INI1, BAF170, and BAF155 in peripheral nerve sheath tumors (especially in sporadic peripheral schwannomas and vestibular schwannomas). We identified a reduced expression of BAF170 in a high percentage of INI1 expressing schwannomas by immunohistochemistry. To characterize the underlying molecular mechanism we furthermore investigated RNA expression, carried out genomic sequencing of the whole BAF170 gene, and performed methylation analysis of the BAF170 promoter. In addition, BAF 170 expression was analysed in various human adult and fetal tissues by immunohistochemistry to understand regulation of gene expression during histogenesis.
In conclusion, we demonstrate a reduced expression of the SWI/SNF-subunit BAF170 in schwannomas and discuss a questionable tumor suppressor role of this essential SWI/SNF subunit.
Supported by Innovative Medizinische Forschung (IMF) (HA121006)