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Thesis Complete-Mufaddal Mustafa.pdf (1.51 MB)

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Alterations in Genomic 5-Hydroxymethylcytosine Level in Hepatocellular Cancer

Mustafa, Mufaddal
http://rave.ohiolink.edu/etdc/view?acc_num=osu1366115027

Abstract Details

2013, Master of Science, Ohio State University, Pathology.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. There are a limited number of therapeutic options currently available to delay the advancement of HCC, and the chance of survival decreases as the disease progresses. DNA methylation of certain tumor suppressor genes and hypomethylation of oncogenes have been shown to initiate HCC. 5-hydroxymethylcytosine (5-hmC), recently identified sixth base of the genome, can cause demethylation by its conversion to cytosine through reactions catalyzed by the TET enzymes. Research on the role of this novel modification in the liver and HCC is needed before it can be therapeutically targeted. To this end, we planned to perform systematic analysis of the role of 5-hmC in liver biology and its aberrations in HCC. In the present study, DNA from primary human HCC and matching benign livers were used to compare alterations in 5-hmC level, if any, in tumors. Mouse models of HCC were also used to further validate the results obtained from human specimens. We observed remarkable decrease in global 5-hmC content in HCCs of both human and rodent origin using multiple techniques that include dot blot, immunohistochemistry, and LC/MS analysis. Furthermore, specific regions of EGFR, H19, and 7SL loci also exhibited reduced 5-hmC levels in the tumor samples. Since aberrations in methylation can cause cancer including HCC, it would be important to identify differentially hydroxymethylated genes in the liver and the consequence of their differential hydroxymethylation in HCC.
Kalpana Ghoshal (Advisor)
Samson Jacob (Committee Member)
49 p.
Biology; Genetics; Molecular Biology; Oncology
5-hmC; methylation; hydroxymethylation; HCC; liver; cancer

Recommended Citations

Citations

  • Mustafa, M. (2013). Alterations in Genomic 5-Hydroxymethylcytosine Level in Hepatocellular Cancer [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366115027

    APA Style (7th edition)

  • Mustafa, Mufaddal. Alterations in Genomic 5-Hydroxymethylcytosine Level in Hepatocellular Cancer. 2013. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1366115027.

    MLA Style (8th edition)

  • Mustafa, Mufaddal. "Alterations in Genomic 5-Hydroxymethylcytosine Level in Hepatocellular Cancer." Master's thesis, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1366115027

    Chicago Manual of Style (17th edition)

osu1366115027
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© 2013, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.