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Updated: Jun 16, 2026

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
[Double strand break of DNA in gastric adenoma and adenocarcinoma]
Jeong Ho Kim1, Sung Soo Kim, Sang Won Byun
1Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea. jkkim488@yahoo.co.kr
Background/Aims:
DNA double strand break (DSB) is one of the critical types of DNA damage. When unrepaired DSB is accumulated in the nucleus of the cells having mutations in such genes as p53, it will lead to chromosomal instability and further more to mutation of tumor-activating genes resulting in tumorogenesis. Some of malignant cancers and its premalignant lesions were proven to have DSB in their nuclei. The aim of this study was to define the differences in expression of 53BP1 and gamma-H2AX, the markers of DSB, among normal, gastric adenoma, and gastric adenocarcinoma tissues.
Methods:
Tissue microarray was made with the tissues taken from 121 patients who underwent gastrectomy for gastric adenocarcinoma, and 51 patients who underwent endoscopic mucosal resection for gastric adenoma. Immunochemical stain was performed for the marker of DSB, 53BP1 and gamma-H2AX in the tissue microarray. The normal tissues were collected from histologically confirmed tissues with no cellular atypia obtained from the patients with gastric adenocarcinoma.
Results:
In gastric carcinoma cells, 53BP1 and gamma-H2AX were highly expressed as compared to normal epithelial cells and gastric adenoma (p<0.01). There were no differences in the expression of 53BP1 and gamma-H2AX between normal epithelium and gastric adenoma. The expression of 53BP1 in the adenoma with grade II and III atypism was more elevated than in those with grade I atypism. The expression of 53BP1 and gamma-H2AX were not significantly different according to the clinicopathologic parameters in the patients with gastric adenocarcinoma.
Conclusions:
The DSB in DNA seems to be associated with the development of gastric adenocarcinoma, but does not affect the premalignant adenoma cells.
Insights
DNA double-strand breaks (DSBs) are linked to gastric cancer development. Researchers found elevated 53BP1 and gamma-H2AX protein expression in gastric adenocarcinoma, but not in premalignant adenoma tissues.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- DNA double-strand breaks (DSBs) are critical DNA damage. Unrepaired DSBs can lead to chromosomal instability and tumorogenesis, especially in p53-mutated cells.
- DSBs have been observed in malignant cancers and premalignant lesions.
- Gastric cancer and its precursor lesions are significant health concerns globally.
Purpose of the Study:
- To investigate the differential expression of 53BP1 and gamma-H2AX, established markers for DSBs.
- To compare the expression levels of these DSB markers in normal gastric tissues, gastric adenomas, and gastric adenocarcinomas.
Main Methods:
- Tissue microarray construction using samples from 121 gastric adenocarcinoma and 51 gastric adenoma patients.
- Immunohistochemical staining for 53BP1 and gamma-H2AX in tissue microarrays.
- Inclusion of normal gastric tissues from gastric adenocarcinoma patients for comparison.
Main Results:
- Significantly higher expression of 53BP1 and gamma-H2AX was observed in gastric carcinoma cells compared to normal and adenoma tissues (p<0.01).
- No significant difference in 53BP1 and gamma-H2AX expression was found between normal epithelium and gastric adenoma.
- Elevated 53BP1 expression correlated with higher atypia grades (II and III) in adenomas.
Conclusions:
- DNA double-strand breaks appear to be associated with the progression to gastric adenocarcinoma.
- DSBs do not seem to significantly impact premalignant adenoma cells.
- These findings suggest DSB markers could play a role in understanding gastric carcinogenesis.
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