Alterations in Genomic 5-Hydroxymethylcytosine Level in Hepatocellular Cancer

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.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Pathology

Grantor dc:publisher

The Ohio State University

Year dc:date

2013

Author dc:creator

• Mustafa, Mufaddal

Contributors dc:contributor

• Ghoshal, Kalpana

• Oncology
• Biology
• Molecular Biology
• Genetics
• 5-hmC
• methylation
• hydroxymethylation
• HCC
• liver
• cancer

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

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

OAI identifier oai:identifier

oai:etd.ohiolink.edu:osu1366115027