Identification of Novel Methylation Markers in Hepatocellular Carcinoma using a Methylation Array.
10.3346/jkms.2010.25.8.1152
- Author:
So Hyun SHIN
1
;
Baek Hui KIM
;
Ja June JANG
;
Kyung Suk SUH
;
Gyeong Hoon KANG
Author Information
1. Laboratory of Epigenetics, Cancer Research Institute and Brain Korea 2nd Stage, Seoul National University, Seoul, Korea. ghkang@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Bead Array;
CpG Islands;
DNA Methylation;
Carcinoma, Hepatocellular
- MeSH:
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
- From:Journal of Korean Medical Science
2010;25(8):1152-1159
- CountryRepublic of Korea
- Language:English
-
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.
