Identifier

etd-06302004-160846

Degree

Master of Science (MS)

Department

Environmental Sciences

Document Type

Thesis

Abstract

Epigenetics is defined as the study of heritable changes of DNA. One such component of epigenetic regulation is DNA methylation in humans. In neoplastic cells epigenetic controls are often dysregulated, especially in the promoter region of CpG islands. Global hypomethylation along with region specific hypermethylation of CpG islands in the promoter region of tumor suppressor is often indicative of neoplastic cells. In cancer, CpG island cytosine hypermethylation has been observed in more than fifty genes, including known tumor suppressor and DNA repair genes. Squamous cell carcinoma (SCC), lichen sclerosis (LS), and adjacent normal tissues were obtained by radical vulvectomies of over one hundred patients. Normal unassociated tissues were also collected in the same manner. The disease process of LS provides an environment conducive to oxidative damage and increases in free radicals. Increased methylation in the promoter regions of specific tumor suppressor and DNA repair genes were anticipated to display a progression to malignancy from normal tissue to LS to SCC. Hypermethylation patterns of p16, p15, O6 methyl guanine methyl transferase (MGMT), glutathione S-transferase pi (GSTP1) were examined by methylation specific polymerase chain reaction (MSP) to obtain an etiological model of vulvar cancer. SCC samples exhibited 26% and 34% methylation in p16 and p15 genes. LS samples displayed 22% and 31% methylation in p16 and p15. The level of hypermethylation in SCC and LS associated samples was significantly different from normal samples in both p16 and p15 genes, suggesting that silencing of these two genes is an early and important event in vulvar squamous cell carcinoma. GSTP1 and MGMT were not found to have a statistically significant difference in any of the tissues tested.

Date

2004

Document Availability at the Time of Submission

Release the entire work immediately for access worldwide.

Committee Chair

Vincent L. Wilson

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