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Identification of novel methylation markers in hepatocellular carcinoma using a methylation array.

Shin SH, Kim BH, Jang JJ, Suh KS, Kang GH - J. Korean Med. Sci. (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Epigenetics, Cancer Research Institute and Brain Korea 2nd Stage, Seoul National University, 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.

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Related in: MedlinePlus

Summary of methylation-specific PCR results in hepatocellular carcinoma (n=50) and non-neoplastic liver tissue samples (n=18). Out of 26 genes showing methylation in HCC cell lines, promoter methylation was detected in 25 genes in primary tumor tissues. Data are color-coded as follows: gray fill indicates the presence of methylation, while white fill indicates absence of methylation.
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Figure 4: Summary of methylation-specific PCR results in hepatocellular carcinoma (n=50) and non-neoplastic liver tissue samples (n=18). Out of 26 genes showing methylation in HCC cell lines, promoter methylation was detected in 25 genes in primary tumor tissues. Data are color-coded as follows: gray fill indicates the presence of methylation, while white fill indicates absence of methylation.

Mentions: To determine whether the genes that were hypermethylated in the HCC cell lines were hypermethylated in a cancer-specific manner, we analyzed the methylation status of the 26 genes in 18 normal liver samples and 50 primary HCC samples using methylation-specific PCR. Of the candidate 26 genes that showed methylation in the cell lines, promoter methylation was detected in 25 of the genes in primary tumor tissues. In contrast, only five genes (5 of 26; 19.2%) were methylated in normal tissues. Moreover, all but one of these genes (IGF2AS) were methylated at low frequencies in the non-neoplastic liver tissues (Fig. 4). Thus, the vast majority of the genes were found to show cancer-specific methylation at frequencies of 6%-98% (Fig. 5). Thus, 24 new cancer-specific CpG island loci were identified through our approach (Table 3).


Identification of novel methylation markers in hepatocellular carcinoma using a methylation array.

Shin SH, Kim BH, Jang JJ, Suh KS, Kang GH - J. Korean Med. Sci. (2010)

Summary of methylation-specific PCR results in hepatocellular carcinoma (n=50) and non-neoplastic liver tissue samples (n=18). Out of 26 genes showing methylation in HCC cell lines, promoter methylation was detected in 25 genes in primary tumor tissues. Data are color-coded as follows: gray fill indicates the presence of methylation, while white fill indicates absence of methylation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2908783&req=5

Figure 4: Summary of methylation-specific PCR results in hepatocellular carcinoma (n=50) and non-neoplastic liver tissue samples (n=18). Out of 26 genes showing methylation in HCC cell lines, promoter methylation was detected in 25 genes in primary tumor tissues. Data are color-coded as follows: gray fill indicates the presence of methylation, while white fill indicates absence of methylation.
Mentions: To determine whether the genes that were hypermethylated in the HCC cell lines were hypermethylated in a cancer-specific manner, we analyzed the methylation status of the 26 genes in 18 normal liver samples and 50 primary HCC samples using methylation-specific PCR. Of the candidate 26 genes that showed methylation in the cell lines, promoter methylation was detected in 25 of the genes in primary tumor tissues. In contrast, only five genes (5 of 26; 19.2%) were methylated in normal tissues. Moreover, all but one of these genes (IGF2AS) were methylated at low frequencies in the non-neoplastic liver tissues (Fig. 4). Thus, the vast majority of the genes were found to show cancer-specific methylation at frequencies of 6%-98% (Fig. 5). Thus, 24 new cancer-specific CpG island loci were identified through our approach (Table 3).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Epigenetics, Cancer Research Institute and Brain Korea 2nd Stage, Seoul National University, 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.

Show MeSH
Related in: MedlinePlus