Dataset Information

Methylation of the Tumor Suppressor Gene RUNX3 in Human Gastric Carcinoma.

ABSTRACT: BACKGROUND/AIMS: RUNX3 (PEBP2alphaC/CBFA3/AML2) is a novel tumor suppressor gene in the human gastric carcinoma. The aims of this study were to determine the methylation of RUNX3 promoter and the association between RUNX3 methylation and the clinicopathological characteristics of patients with gastric carcinoma. METHODS: Seventy-nine patients with gastric carcinoma were studied prospectively from April 2005 to May 2007. The methylations of RUNX3 promoter on the gastric carcinoma specimens and the corresponding nonneoplastic mucosa were evaluated by methylation-specific polymerase chain reaction. RESULTS: Comparison of the results with the clinicopathological characteristics identified RUNX3 monoallelic methylation in 32.9% (26/79) of the gastric carcinoma patients and in 11.4% (9/79) of those with nonneoplastic mucosa (p=0.053). The monoallelic methylated gastric carcinoma specimens predominantly consisted of well- and moderately differentiated carcinomas (44.7%), with the unmethylated group constituting 22.0% of them (p=0.031). Among the 48 patients (60.8%) who underwent gastrectomy, there was no correlation between the two groups with regard to Lauren's classification (p=0.235), depth of invasion (p=0.990), nodal status (p=0.601), stage (p=0.900), lymphatic invasion (p=0.537), and vascular invasion (p=0.815). CONCLUSIONS: Methylation of the tumor suppressor gene RUNX3 might be one of the mechanisms involved in the pathogenesis of gastric carcinoma.

SUBMITTER: Song HJ

PROVIDER: S-EPMC2871588 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Methylation of the Tumor Suppressor Gene RUNX3 in Human Gastric Carcinoma.

Song Hyun Joo HJ Shim Ki-Nam KN Joo Yang-Hee YH Kim Seong-Eun SE Jung Sung-Ae SA Yoo Kwon K

Gut and liver 20080930 2

<h4>Background/aims</h4>RUNX3 (PEBP2alphaC/CBFA3/AML2) is a novel tumor suppressor gene in the human gastric carcinoma. The aims of this study were to determine the methylation of RUNX3 promoter and the association between RUNX3 methylation and the clinicopathological characteristics of patients with gastric carcinoma.<h4>Methods</h4>Seventy-nine patients with gastric carcinoma were studied prospectively from April 2005 to May 2007. The methylations of RUNX3 promoter on the gastric carcinoma spe ...[more]

PMID: 20485621

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Project description:BackgroundThe caspase-associated recruitment domain-containing protein (CARP) is expressed in almost all tissues. Recently, the tumor-suppressive function of CARP was discovered and attracted increasing attention. This study aimed to investigate the role of CARP in the carcinogenesis of human gastric carcinoma.Methodology/principal findingsCompared with normal gastric tissue, the downregulation of CARP expression was observed in gastric carcinoma tissue by cDNA array and tissue microarray assay. In vitro, the gastric carcinoma cell line (BGC-823) was stably transfected with pcDNA3.1B-CARP or plus CARP siRNA, and we used MTT, flow cytometry, cell migration on type I collagen, cell-matrix adhesion assay and western blot analysis to investigate the potential anti-tumor effects of CARP. The data showed that overexpressing CARP suppressed the malignancy of gastric carcinoma BGC-823 cell line, including significant increases in apoptosis, as well as obvious decreases in cell proliferation, migration, adhesion ability, and tumor growth. The tumor-suppressive effects of CARP were almost restored by siRNA-directed CARP silence. In addition, overexpression of CARP induced G1 arrest, decreased the expressions of cyclin E and CDK2, and increased the expressions of p27, p53 and p21. In vivo, the tumor-suppressive effect of CARP was also verified. A single-nucleotide polymorphism (SNP) genotype of CARP (rs2297882) was located in the Kozak sequence of the CARP gene. The reporter gene assay showed that rs2297882 TT caused an obvious downregulation of activity of CARP gene promoter in BGC-823 cells. Furthermore, the association between rs2297882 and human gastric carcinoma susceptibility was analyzed in 352 cases and 889 controls. It displayed that the TT genotype of rs2297882 in the CARP gene was associated with an increased risk of gastric carcinoma.Conclusions/significanceCARP is a potential tumor suppressor of gastric carcinoma and the rs2297882 C>T phenotype of CARP may serve as a predictor of gastric carcinoma.

Dataset Information

Methylation of the Tumor Suppressor Gene RUNX3 in Human Gastric Carcinoma.

Publications

Methylation of the Tumor Suppressor Gene RUNX3 in Human Gastric Carcinoma.

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