Date of Award
Master of Science (MS)
Cancer is one of the most prominent diseases resulting in death, thus the need for early detection remains essential to its treatments. It is usually associated with DNA methylation changes during tumorigenesis. While many studies focus on euchromatin, some studies have looked at the methylation changes in heterochromatin, since the methylation changes of repetitive elements is common and they contribute to karyotypic instability leading to enhanced chances for more mutations in tumor progression. Using bisulfite PCR and HC21 as a model, this study examines the DNA methylation changes of three repetitive elements in prostate cancer, NBL2, satellite I subfamilies, and gamma satellite. NBL2 is a 1.4 kb tandem repeat located on chromosomes 9, 13, 14, 15, and 21. A previous study of NBL2 suggested that it is located near the centromeres and it can be either hypo or hypermethylated in cancer, making it tumor-specific. Results from this study using hybrid cell mapping and mapping via Genome Browser suggest that NBL2 is located 1Mb farther from the centromere than previously thought. Preliminary data indicates that NBL2 is not a viable biomarker for prostate cancer due to its high methylation patterns across all cell templates used. Satellite I subfamilies methylation patterns were not examined due to the failed amplification process. Gamma satellite is a tandem array that contains 220bp GC-rich repeating units that can form 10-200 kb clusters found in the pericentromeric regions of all chromosomes. Previous studies suggest that gamma has an anti-silencing activity to prevent the spread of heterochromatin into the long arm, and it is hypermethylated in cancer. This study found gamma satellite to be hypermethylated in prostate cancer and normal cells. This suggests that the stable DNA methylation of gamma satellite may play a major role in the anti-silencing boundary rather than histone modifications. Overall, both NBL2 and gamma satellite do not seem to be potential biomarkers for prostate cancer due to their stable hypermethylation patterns in different cell types.
Neang, Navy, "DNA Methylation Patterns of Repetitive Elements on HC21" (2020). Master's Theses. 4374.
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