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Updated: Jun 11, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
CpG methylation of transcription factor 4 in gastric carcinoma
Jae Kyoon Joo1, Sang Hyun Kim, Ho Gun Kim
1Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
Background:
Epigenetic silencing of tumor-related genes by CpG island methylation is an important mechanism for the development of many tumors, including gastric carcinoma. Deregulation of transcription factor 4 (TCF4) by promoter methylation was recently shown to play a key role in gastric carcinogenesis.
Methods:
The extent of methylation in the TCF4 promoter was assessed using methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PS) in 120 gastric carcinoma (GC) samples collected during gastrectomy, and in 40 normal gastric mucosa samples.
Results:
The PS analysis of GCs revealed a higher frequency of TCF4 methylation (75.8%; 91/120). The methylation frequency for TCF4 by both MSP and PS techniques was significantly higher in advanced (75.0 and 91.7%, respectively) compared with early (60.0 and 60.0%, respectively, p < 0.05) GCs. There was a significant difference in TCF4 methylation between GCs and normal gastric mucosa (67.5 vs. 40.0%, respectively, by MSP and 75.8 vs. 30.0%, respectively, by PS; p < 0.05). There was significant correlation between TCF4 methylation status by PS and tumor size (p = 0.004), Lauren classification (p = 0.043), depth of invasion (p < 0.001), nodal metastasis (p = 0.021), and tumor-node-metastasis (TNM) stage (p = 0.045).
Conclusions:
These results suggest that inactivation of TCF4 by promoter methylation may play a role in the early stage of gastric carcinoma progression. Furthermore, standard polymerase chain reaction followed by PS may provide a more specific and quantitative diagnostic alternative to MSP, which may be of benefit in oncology research.
Insights
Epigenetic silencing of the TCF4 gene via promoter methylation is frequent in gastric cancer, particularly in advanced stages. This methylation may drive early gastric carcinoma progression, with pyrosequencing offering a precise diagnostic tool.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- CpG island methylation epigenetically silences tumor-related genes in cancers like gastric carcinoma.
- Promoter methylation of transcription factor 4 (TCF4) is implicated in gastric carcinogenesis.
Purpose of the Study:
- To investigate the frequency and significance of TCF4 promoter methylation in gastric cancer.
- To compare methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PS) for TCF4 methylation assessment.
Main Methods:
- Assessed TCF4 promoter methylation using MSP and PS in 120 gastric carcinoma (GC) and 40 normal gastric mucosa samples.
- Correlated methylation status with clinicopathological features.
Main Results:
- TCF4 methylation was detected in 75.8% of GCs, significantly higher than in normal mucosa (p < 0.05).
- Methylation frequency increased with tumor advancement and correlated significantly with tumor size, Lauren classification, invasion depth, nodal metastasis, and TNM stage (p < 0.05).
Conclusions:
- TCF4 inactivation by promoter methylation may contribute to early gastric carcinoma progression.
- Pyrosequencing offers a more specific and quantitative diagnostic alternative to MSP for oncology research.
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