DNA Hypermethylation of Tumor-Related Genes in Gastric Carcinoma

Hong, Su Hyung; Kim, Ho Gak; Chung, Woon Bok; Kim, Eun Young; Lee, Jong‐Young; Yoon, Sang Mo; Kwon, Joong Goo; Sohn, Yoon Kyung; Kwak, Eun Kyung; Kim, Jung Wan

doi:10.3346/jkms.2005.20.2.236

Cited by 27 publications

(21 citation statements)

References 24 publications

(25 reference statements)

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“…In our study, we investigated the prognostic value of IL-6 in gastric cancer and analyzed the associations of serum level of IL-6 with methylation status of p16, DAPK, MGMT, and E-cadherin, which represent genes involved in the important steps of tumorigenesis including cell cycle regulation, DNA repair, apoptosis and metastasis. Promoters of these genes have been suggested to be hypermethylated in gastric cancers and play important roles in gastric carcinogenesis [10,11,12]. We aimed at further confirming the prognostic role of IL-6 in gastric cancer and investigating if there was any association between serum IL-6 and methylation of gastric cancer which could indirectly provide us with more ideas to understand the working mechanisms and mutual relationship of IL-6 and tumor cells.…”

Section: Introductionmentioning

confidence: 99%

An Inverse Correlation between Interleukin-6 and Select Gene Promoter Methylation in Patients with Gastric Cancer

et al. 2006

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Background: Both serum IL-6 levels and CpG island methylation have been shown to have prognostic significance in gastric cancer, it was suggested that an important link existed between IL-6 and methylation of cancers. Aim: To investigate the prognostic value of IL-6 serum level and the association between serum IL-6 levels and CpG island methylation at p16, DAPK, MGMT and E-cadherin in patients with gastric cancer. Patients and Methods: Methylation status was assessed by MSP in 75 surgical specimens of gastric adenocarcinoma. IL-6 serum levels were measured by chemiluminescent enzyme immunoassay (CLEIA). Results: Methylation of p16, DAPK, MGMT, and E-cadherin were present in 53, 48, 32, and 59% of patients. Patients with tumors methylated at p16 and DAPK had lower serum levels of IL-6 compared to unmethylated tumors (1.8 vs. 4.8 pg/ml, p = 0.01 for p16; 1.5 vs. 6.2 pg/ml, p = 0.0001 for DAPK). But there was no difference with MGMT and E-cadherin methylation status. Serum IL-6 levels were also associated with TNM stage (p = 0.001), depth of tumor invasion (p = 0.002), lymphatic invasion (p = 0.01), vascular invasion (p = 0.008), metastasis (p = 0.002) and signet cell histology (p = 0.001). Conclusion: IL-6 is of prognostic value for patients of gastric cancer. Low serum IL-6 levels were associated with p16 or DAPK gene methylation in patients with gastric cancer.

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Section: Introductionmentioning

confidence: 99%

An Inverse Correlation between Interleukin-6 and Select Gene Promoter Methylation in Patients with Gastric Cancer

et al. 2006

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“…In GAs, loss of Mlh1 expression was detected in only three tumors of elderly female patients. while three studies have indicated a trend of association between female gender and immunohistochemical negativity for Mlh1 or for the MSI phenotype in GCs, the samples used in these studies were surgical tissues (13,36,37). The results from these studies suggest differences between the genders in the molecular pathways of gastric neoplasia in elderly patients.…”

Section: Mlh1 Expressionmentioning

confidence: 72%

“…Numerous GCs develop through defects in DNA MMR genes, such as MLH1 or MSH2, or tumor suppressor genes, such as P53 (12). Evidence of MLH1 hypermethylation is noted in approximately 20-30% of differentiated carcinomas (11)(12)(13). Epigenetic methylation-associated inactivation of the MLH1 MMR gene is a potent trigger of MSI, especially high-frequency MSI (MSI-H) (17).…”

Section: Discussionmentioning

confidence: 99%

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Clinicopathological and patient characteristics of early gastric neoplasia endoscopically resected with loss of Mlh1 expression

Sasaki

Yashima

Hayashi³

et al. 2010

Oncology Letters

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Abstract. Hypermethylation of the promoter region of the MLH1 gene leads to loss of Mlh1 protein expression and plays a key role in the development of gastric cancer. Little is known about the association between Mlh1 expression and the clinicopathological and patient characteristics in early gastric neoplasia, particularly in endoscopically resected tumors. Immunohistochemistry was used to examine Mlh1 expression in 140 early gastric neoplasias obtained by endoscopic resection and comprising 31 gastric adenomas (GAs) and 109 early gastric cancers (EGCs), and compared them to corresponding clinicopathological and patient data. P53 expression and phenotypic profiles were also analyzed. The rate of reduced Mlh1 expression and P53 overexpression was 9.6 and 6.5% in GAs, and 27.5 and 27.5% in EGCs, respectively. In elderly patients (≥65 years of age), the aberrant expression of Mlh1 in EGCs was more significant in female than in male patients (59.9 vs. 29.8%; P=0.016). In addition, the frequency of aberrant Mlh1 expression in EGCs increased significantly in patients with oncological family histories and elevated gross type (P=0.033 and P=0.04, respectively). Moreover, a significant correlation was observed among aberrant Mlh1, P53-negative and HGM expression. The present findings suggest that loss of Mlh1 expression is associated with age, gender, oncological family history and tumor growth pattern in EGC. Patient and tumor characteristics are key factors in the screening, surveillance and diagnosis of early gastric neoplasia, particularly in elderly individuals.

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“…hMLH1 pro tein coding gene is a member of the family of pro teins required for DNA mismatch repair (6). Many studies confirmed the hMLH1 gene function loss by promoter methylation in gastric cancer (7)(8)(9)(10)(11)(12). There is data that hMLH1 methylation is associated with stomach intestinal carcinoma type (7) and this epigenetic event occurs in early gastric cancer (8).…”

Section: Introductionmentioning

confidence: 71%

Frequency of gene hMLH1 promoter methylation in the stomach antral and body area tissue of chronic atrophic pangastritis patients

Kupčinskaitė-Noreikienė¹,

Jančiauskas²,

Juozaitytė³

2013

AML

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Aim.To compare hMLH1 methylation frequency in stomach antral and body area tissue in chronic atrophic pangastritis patients, and to evaluate possible correlation severity of chronic atrophic gastritis markers.Methods. The study population consisted of 24 participants (with histologically confirmed chronic atrophic pangastritis), who underwent upper endoscopy. Biopsy specimens were taken from the gastric antral and body area. The methylation status of the gene hMlH1 was investigated.Results. Methylation of the CpG island of gene hMLH1 was found in the antral stomach area group 9/24, compared with the body area 2/24. There was a significant difference in gene methylation frequencies in the observed stomach parts (Fisher's exact test, p = 0.04). There was a significant association between gene hMLH1 methylation and the occurrence of severe atrophic gastritis, intestinal metaplasia and the presence of hyperplastic mucosal changes (Fisher's exact test, p < 0.05).Conclusions. hMLH1 gene methylation frequency is higher in the stomach antral tissue compared with the stomach body tissue, and increases with higher level of atrophic gastritis and intestinal metaplasia.

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DNA Hypermethylation of Tumor-Related Genes in Gastric Carcinoma

Cited by 27 publications

References 24 publications

An Inverse Correlation between Interleukin-6 and Select Gene Promoter Methylation in Patients with Gastric Cancer

An Inverse Correlation between Interleukin-6 and Select Gene Promoter Methylation in Patients with Gastric Cancer

Clinicopathological and patient characteristics of early gastric neoplasia endoscopically resected with loss of Mlh1 expression

Frequency of gene hMLH1 promoter methylation in the stomach antral and body area tissue of chronic atrophic pangastritis patients

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