ABERRANT DNA METHYLATION IN HEPATOCELLULAR CARCINOMA

Abstract

Hepatocellular Carcinoma (HCC) is one of the most common human cancers in the world. Despite its high mortality rate, molecular pathogenesis of HCC remained unclear. In this thesis, the implications of aberrant DNA methylation in HCC were elucidated. Methylation profiling of 59 HCC patients were carried out with Infinium Methylation27 platform. We identified 4416 differentially methylated CpG loci that separate tumors from adjacent non-tumorous tissues. When methylation data was integrated with gene expression profile, we found 536 deregulated genes. These genes were enriched in inflammation pathway according to Ingenuity Pathway Analysis. Using this integrated data, we also uncovered methylated gene, CYB5R2 that may be involved in hepatocarcinogenesis. Lastly, we subdivided tumors into different subgroups based on methylation clustering. One group of patients exhibited worse survival outcomes compared to the rest of the patients. Overall, methylation profile provides another layer of understanding on the aberrant epigenetic mechanism underlying HCC.