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Updated: Jun 13, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
BCL2L10 is frequently silenced by promoter hypermethylation in gastric cancer
Rintaro Mikata1, Kenichi Fukai, Fumio Imazeki
1Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Abstract:
In gastric cancer, several tumor suppressor and tumor-related genes are silenced by aberrant methylation. Previously, we demonstrated that BCL2L10, which belongs to the pro-apoptotic Bcl-2 family, was transcriptionally repressed by promoter hypermethylation and that its overexpression caused apoptosis and growth inhibition of gastric cancer cells. In this study, we investigated the methylation status of BCL2L10 and its expression in 21 gastric cancer tissues and corresponding non-neoplastic mucosae along with the methylation status of p16, RUNX3, and hMLH1 genes by using methylation specific PCR. In addition, we examined the association between the methylation status of each gene and the expression of EZH2, which was associated with DNA methylation of its target genes. As a result, aberrant methylation of BCL2L10 was detected in 38% of gastric cancer and in 24% of corresponding non-neoplastic mucosae and correlated with low expression of BCL2L10. Methylation of p16, RUNX3, and hMLH1 was found in gastric cancer and in corresponding non-neoplastic mucosae at almost similar frequencies as previous reports. Expression of EZH2 was detected more frequently in tumors (48%) as compared to corresponding non-neoplastic mucosae (10%) (p=0.006), however, no significant difference was found between expression of EZH2 and the methylation frequency of each gene. In conclusion, our data suggest that silencing of BCL2L10 by aberrant methylation is a common feature in gastric cancer and its inactivation may be involved in the early steps of gastric carcinogenesis.
Insights
Aberrant methylation silences the BCL2L10 gene in gastric cancer, potentially contributing to tumor development. This gene silencing correlates with reduced BCL2L10 expression, suggesting its role in early gastric carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Aberrant methylation frequently silences tumor suppressor genes in gastric cancer.
- BCL2L10, a pro-apoptotic gene, was previously shown to be repressed by promoter hypermethylation in gastric cancer cells.
Purpose of the Study:
- To investigate the methylation status and expression of BCL2L10 in gastric cancer tissues.
- To examine the methylation status of p16, RUNX3, and hMLH1 in gastric cancer.
- To assess the association between gene methylation and EZH2 expression in gastric cancer.
Main Methods:
- Methylation-specific PCR was used to analyze the methylation status of BCL2L10, p16, RUNX3, and hMLH1 in 21 gastric cancer tissues and corresponding non-neoplastic mucosae.
- Gene expression levels were assessed.
- The association between gene methylation and EZH2 expression was examined.
Main Results:
- Aberrant BCL2L10 methylation was found in 38% of gastric cancers and 24% of non-neoplastic mucosae, correlating with low BCL2L10 expression.
- Methylation frequencies for p16, RUNX3, and hMLH1 were consistent with previous reports.
- EZH2 expression was significantly higher in tumors (48%) than in non-neoplastic mucosae (10%), but no significant correlation was found with the methylation of the studied genes.
Conclusions:
- Silencing of BCL2L10 by aberrant methylation is a common event in gastric cancer.
- BCL2L10 inactivation may play a role in the early stages of gastric carcinogenesis.
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