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68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
7. Joint Meeting mit der Britischen Gesellschaft für Neurochirurgie (SBNS)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

14. - 17. Mai 2017, Magdeburg

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Genes and molecular pathways involved in radioresistance of sporadic and NF2-associated vestibular schwannomas: a microarray and pathway analysis

Meeting Abstract

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  • Isabel Gugel - Klinik für Neurochirurgie, Universitätsklinikum Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Deutschland
  • Florian Ebner - Klinik für Neurochirurgie, Universitätsklinikum Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Deutschland
  • Frank Paulsen - Klinik für Radioonkologie, Universitätsklinikum Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Deutschland
  • Stefan Czemmel - Zentrum für Quantitative Biologie, Eberhard Karls Universität Tübingen, Tübingen, Deutschland
  • Sven Nahnsen - Zentrum für Quantitative Biologie, Eberhard Karls Universität Tübingen, Tübingen, Deutschland
  • Marcos Tatagiba - Klinik für Neurochirurgie, Universitätsklinikum Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Deutschland
  • Ghazaleh Tabatabai - Interdisziplinäre Sektion Neuroonkologie, Hertie Institut für Klinische Hirnforschung, Universitätsklinikum Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Deutschland

Deutsche Gesellschaft für Neurochirurgie. Society of British Neurological Surgeons. 68. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 7. Joint Meeting mit der Society of British Neurological Surgeons (SBNS). Magdeburg, 14.-17.05.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocDI.13.06

doi: 10.3205/17dgnc252, urn:nbn:de:0183-17dgnc2523

Veröffentlicht: 9. Juni 2017

© 2017 Gugel et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Objective: Vestibular schwannomas (VSs) are benign tumors of the eighth cranial nerve which occur either as sporadic unilateral tumors or bilateral as a hallmark of neurofibromatosis type 2 (NF2). Besides microsurgical resection or chemotherapy in case of NF2-associated VSs, more recently stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) have gained acceptance as effective alternatives. However, there is a subset of radioresistant tumors that continue to grow after radiation treatment. Radioresistant behavior at the molecular level as well as the differences between irradiated sporadic and NF2-associated VSs are not well understood. The objective of this study was to provide insight into the radiobiology of sporadic and NF2-associated VSs through gene expression profiling and pathway analysis.

Methods: 49 non-irradiated and 7 irradiated recurrent VS tumors were fresh-frozen at the time of surgical resection and RNA isolation was performed for cDNA microarray analysis (HG-U219 Array Plate, Affymetrix®). We utilized canonical pathway analysis (Ingenuity Pathway Analysis) to investigate pathways involved in radioresistance.

Results: A total of 195 probe sets (128 probe sets were up- and 67 downregulated) showed significant difference based on the criteria of P value < 0.01 and absolute fold change ≥ 2. These genes were involved in deregulation of important pathways known to be involved in radioresistance (e.g. NF-κB Signaling, STAT3 signaling, p53 signaling, ect.) resulting in proliferation, hypoxia, angiogenesis and cell cycle interruption.

Conclusion: Irradiated sporadic and NF2-associated tumors share common modifications of pathways which contribute to radioresistance in tumors and could be a reason for acquired resistance to radiation. These pathways and their participating genes might function as candidate therapeutic targets for radiosensitizers in the future.