J Korean Med Sci.  2010 Aug;25(8):1152-1159. 10.3346/jkms.2010.25.8.1152.

Identification of Novel Methylation Markers in Hepatocellular Carcinoma using a Methylation Array

Affiliations
  • 1Laboratory of Epigenetics, Cancer Research Institute and Brain Korea 2nd Stage, Seoul National University, Seoul, Korea. ghkang@snu.ac.kr
  • 2Department of Pathology, Korea University Medical School, Seoul, Korea.
  • 3Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
  • 4Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.

Abstract

Promoter CpG island hypermethylation has become recognized as an important mechanism for inactivating tumor suppressor genes or tumor-related genes in human cancers of various tissues. Gene inactivation in association with promoter CpG island hypermethylation has been reported to be four times more frequent than genetic changes in human colorectal cancers. Hepatocellular carcinoma is also one of the human cancer types in which aberrant promoter CpG island hypermethylation is frequently found. However, the number of genes identified to date as hypermethylated for hepatocellular carcinoma (HCC) is fewer than that for colorectal cancer or gastric cancer, which can be attributed to fewer attempts to perform genome-wide methylation profiling for HCC. In the present study, we used bead-array technology and coupled methylation-specific PCR to identify new genes showing cancer-specific methylation in HCC. Twenty-four new genes have been identified as hypermethylated at their promoter CpG island loci in a cancer-specific manner. Of these, TNFRSF10C, HOXA9, NPY, and IRF5 were frequently hypermethylated in hepatocellular carcinoma tissue samples and their methylation was found to be closely associated with inactivation of gene expression. Further study will be required to elucidate the clinicopathological implications of these newly found DNA methylation markers in hepatocellular carcinoma.

Keyword

Bead Array; CpG Islands; DNA Methylation; Carcinoma, Hepatocellular

MeSH Terms

Antimetabolites, Antineoplastic/therapeutic use
Azacitidine/analogs & derivatives/therapeutic use
Carcinoma, Hepatocellular/drug therapy/*genetics
Cell Line, Tumor
CpG Islands
*DNA Methylation
GPI-Linked Proteins/genetics
Gene Expression Profiling
Homeodomain Proteins/genetics
Humans
Interferon Regulatory Factors/genetics
Liver Neoplasms/drug therapy/*genetics
Neuropeptide Y/genetics
Oligonucleotide Array Sequence Analysis
Promoter Regions, Genetic
Tumor Necrosis Factor Decoy Receptors/genetics
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