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Vestibular schwannoma: dissecting the pathologic process and clinical applications

Welling, Duane Bradley
http://rave.ohiolink.edu/etdc/view?acc_num=osu1053706721

Abstract Details

2003, Doctor of Philosophy, Ohio State University, Pathology.
Vestibular schwannomas continue to cause significant morbidity including hearing loss, facial nerve paralysis, brainstem compression and death. Although the gene responsible for maintaining tumor suppression in vestibular schwannomas has been identified, understanding of the mechanism of action of this Neurofibromatosis type 2 (NF2) gene has not yet been sufficient to allow application to clinical treatment. This dissertation presents three related investigations. The first is a characterization of the promoter sequence of the NF2 gene, which may be important both in mutation analysis and in tissue specific direction for modeling and treatments. The second investigation is the cDNA microarray analysis of expression of genes in vestibular schwannomas when compared to a normal nerve tissue. The third set of experiments examine one specific pathway, the retinoblastoma pathway, identified in the second investigation, and the role it plays in the development of vestibular schwannomas. The first experiment using NF2 promoter-luciferase constructs demonstrated both positive and negative regulatory elements in the 5’ untranslated region of the NF2 gene. The identified NF2 promoter region is now being tested for tissue specificity and mutational analysis. The cDNA microarray investigation identified 42 which were up regulated 3-fold or more when compared to a normal adjacent vestibular nerve. Among them, genes important in angiogenesis and cell signaling were identified. Among genes that were down regulated, an apoptosis-related LUCA-15 gene was highly under expressed in schwannomas when compared to the normal nerve. In the last set of experiments, expression profiles of eight vestibular schwannomas were chosen and genes from the retinoblastoma-CDK pathway were examined. Among them, CDK2 was substantially under expressed in 7 of the 8 tumors examined. Real-time polymerase chain reaction and immunohistochemistry supported these findings. Taken together, the above data demonstrates that important regulatory elements exist in the 5’ regions of the NF2 gene and that in addition to the NF2 gene, other genes are deregulated within vestibular schwannomas including cell cycle regulators and other putative tumor suppressor genes. These findings provide fertile ground for further exploration aimed toward eventual improved treatment options.
Long-Sheng Chang (Advisor)
Biology, Molecular
Vestibular schwannoma; acoustic neuroma; gene regulation; promoter; microarray; real time pcr; immunohistochemistry

Recommended Citations

Citations

  • Welling, D. B. (2003). Vestibular schwannoma: dissecting the pathologic process and clinical applications [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1053706721

    APA Style (7th edition)

  • Welling, Duane. Vestibular schwannoma: dissecting the pathologic process and clinical applications. 2003. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1053706721.

    MLA Style (8th edition)

  • Welling, Duane. "Vestibular schwannoma: dissecting the pathologic process and clinical applications." Doctoral dissertation, Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1053706721

    Chicago Manual of Style (17th edition)

osu1053706721
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© 2003, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.