Honors Capstone Project
Date of Submission
Dr. Frank Middleton
Dr. Shannon Novak
Arts and Science
Capstone Prize Winner
Won Capstone Funding
Sciences and Engineering
Biology | Genetics and Genomics
Introduction: Glioblastoma multiforme (GBM) is one of the deadliest forms of brain cancer, and affects more than 18,000 new cases each year in the United States alone. The current standard of treatment for GBM includes surgical removal of the tumor, along with radiation and chemotherapy. Despite these treatments, recurrence of GBM is extremely common, and once it recurs, the life expectancy is measured in weeks or months. One of the reasons for the deadly nature of the recurrent GBM is thought to be selection for therapy-resistant tumor cells. In this project, we sought to characterize the molecular changes in recurrent GBM specimens compared to primary GBM specimens from the same subjects.
Methods: Whole-genome DNA microarrays were used to identify genes changed in mRNA expression in seven recurrent GBM samples compared to seven primary GBM samples from the same subjects. Real-time quantitative RT-PCR was used in an attempt to validate changes seen by microarray for 18 genes of interest chosen from the microarray screen.
Results: The microarray experiments identified several dozen mRNA transcripts with evidence of significant differences in expression. From these genes, we chose 18 for PCR validation. Overall, the PCR experiments validated the microarray findings quite well. There was a very high correlation for the magnitude of expression changes seen for the 18 genes (Pearson’s R = 0.852, P < 0.001). Individually, 13 of the 18 genes showed statistically significant changes by PCR in the recurrent versus primary tumor pairs. Of the 5 genes that did not validate at the P<0.05 level, 4 showed trends in the direction predicted by the microarray, while 1 gene did not.
Conclusion: Real time PCR has proven useful for validating changes in recurrent GBMs that could have important clinical applications.
Shah, Anushi, "Molecular Analysis of the Genetic Heterogeneity Between Primary and Recurrent Glioblastoma" (2009). Syracuse University Honors Program Capstone Projects. 449.
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