Title page for ETD etd-07112006-192620
|Type of Document
||Studies of Epigenetic Instability in Human Normal and Diseased Vulva Skin
||Master of Science (M.S.)
|Vincent Lee Wilson
|William R Lee
- histone deacetylation
- histone acetylation
- histon modification
|Date of Defense
Epigenetic modification is another mechanism involved in the cancer development besides classic mutations such as deletion. Aberrant promoter methylation and associated chromatin modification have been frequently reported in various tumors of different clinical stages. Hypermethylation has been frequently observed in tumor suppressor genes and causes reduced transcripts of these genes. Hypomethylation also has been reported to be involved in activation of oncogenes. Inactivation of the X chromosome and the imprinting of gamete DNA depend on the methylation patterns in the promoter region. Understanding methylation mechanisms could be helpful to diagnosis of early stage tumorgenesis or offer molecular markers for detecting cancers.
Changes in methylation patterns based on human vulva pathological tissue type of four genes have been studied in the current project. RASSF1A and DAPK-1 are tumor suppressor genes. BRCA2 is considered highly associated with breast and ovarian cancer. And H19 is a maternal imprinted gene. DAPK-1 and BRCA2 have been found to be significantly hypermethylated in Lichen Sclerosis (LS) and Squamous Cell Carcinoma (SCC). And RASSF1A has displayed an interesting methylation pattern in the post transcription region, where the frequency of methylation significantly decreased from normal tissue to LS tissue, but then dramatically increased to SCC. H19 failed to show any changes in the methylation pattern with methods tested. This was most likely due to interference of primer dimers by SYBR-green in the real-time PCR analyses.
Instead of using the same promoter sequence reported by previous papers, extended estimated promoter regions and partial transcription regions were obtained from Genome Browser and additional CpG island sites have been studied in current project. Methylation patterns have been detected that differ from the literature in these genes. These results may provide more information to find a more precise active promoter region and epigenetic involved sequences for future research.
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