Graduation Date

Fall 12-15-2017

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Genetics, Cell Biology & Anatomy

First Advisor

Chittibabu Guda

Abstract

Glioblastoma (GBM) is the most common and the deadliest type of primary brain tumor, with a median survival time of only 15 months despite aggressive treatment. Although most patients have an extremely poor prognosis, a small number of patients survive far beyond the median survival time. Investigation of these “exceptional responders” has sparked a great deal of interest and is becoming an important focus in the field of cancer research. To investigate the molecular differences between typical and exceptional responders in GBM, comparative analyses of copy number, methylation, gene expression, miRNA expression, and protein expression data sets from The Cancer Genome Atlas were performed, and the results of these analyses were integrated via correlation studies and pathway analyses to assess the functional significance of the differential aberrations. Typical responders are characterized by upregulation of NF-κB signaling and of pro-inflammatory cytokines and their associated pathways, while exceptional responders are characterized by upregulation of Alzheimer’s and Parkinson’s disease pathways, as well as of genes involved in synaptic transmission and plasticity. The upregulated pathways and processes in typical responders are consistently associated with more aggressive tumor phenotypes, while those in the exceptional responders suggest a retained ability in tumor cells to undergo cell death.

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