CpG Island M`ethylation Status in Gastric Carcinoma with and without Infection of Epstein-Barr Virus

Chang, Moon-Sung; Uozaki, Hiroshi; Chong, Ja-Mun; Ushiku, Tetsuo; Sakuma, Kazuya; Ishikawa, Shunpei; Hino, Rumi; Barua, Rita Rani; Iwasaki, Yoshiaki; Arai, Kuniyoshi; Fujii, Hideki; Nagai, Hideo; Fukayama, Masashi

doi:10.1158/1078-0432.ccr-05-1601

Cited by 187 publications

(146 citation statements)

References 23 publications

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“…In several studies, many authors have indicated the existence of a mechanistic linkage between DNA methylation and infection agents. 11,22,[38][39][40][41] This observation has prompted us to suggest the analysis of the relation between JCV infection and the heritable loss related to promoter hypermethylation. To our knowledge, no study has assessed the relationship between JCV-associated gastric carcinomas and the methylation of tumor-related genes.…”

Section: Discussionmentioning

confidence: 99%

The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes

et al. 2010

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JC virus (JCV) is a neurotropic polyomavirus and the causative agent of progressive multifocal leukoencephalopathy. A role for JCV in gastrointestinal malignancies has been recently suggested. This study was carried out to determine the prevalence of polyomaviruses including JCV, BKV and SV40 in gastric cancers in Tunisia and to determine the clinicopathological characteristics of virus-associated gastric carcinomas. The presence of polyomaviruses DNA sequences was surveyed in 61 cases of primary gastric carcinomas and in 53 paired non-tumor gastric mucosa by PCR. Findings were correlated to clinicopathological parameters, p53 expression and methylation status of 11 tumor-related genes. Using PCR assays, JCV T-antigen sequence was more frequently detected in gastric carcinomas than in non-tumor gastric mucosa (26 vs 6%, P ¼ 0.03), while those of SV40 and BKV were not detected in any cases. Correlation analysis showed that JCV had higher frequency in patients older than 55 years (P ¼ 0.034) and in the intestinal histological type (P ¼ 0.04). With regard to methylation status, P16 and P14 showed significantly higher methylation frequencies in JCV-positive gastric carcinomas than in JCV-negative cases (P ¼ 0.007 and P ¼ 0.003, respectively). Moreover, the mean of the methylation index was significantly higher in JCV-positive than in JCV-negative cases (P ¼ 0.024). In multivariate logistic regression analysis, age of patients and the methylation index are only the two independent factors associated with JCV infection. Kaplan-Meier survival analysis showed a trend toward better survival for JCV-associated gastric carcinomas patients (log-rank, P ¼ 0.11). Our study suggests a role of JCV as cofactor in the pathogenesis of the intestinal type of gastric carcinomas in older persons.

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Section: Discussionmentioning

confidence: 99%

The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes

et al. 2010

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“…[21][22][23]30,32,33 However, these previous studies used a small number of CpG island loci by MSP. In our study analyzing 27 CpG island loci by MethyLight, which overcomes some variability problems of MSP, the average MI of EBV-positive GCs and MSI-positive GCs was 0.98 and 0.48, respectively, whereas that of GCs negative for both was 0.37.…”

Section: Methylation In Gc Was Revealed For the First Time In Thismentioning

confidence: 99%

DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis

Kang

Lee

Cho

et al. 2008

Laboratory Investigation

153

107

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Transcriptional silencing by CpG island hypermethylation is a potential mechanism for the inactivation of tumor-related genes. Virtually, all types of human cancers show CpG island hypermethylation, and gastric carcinoma (GC) is one of the tumors with a high frequency of aberrant CpG island hypermethylation. In this study, we prescreened DNA methylation of 170 CpG island loci in a training set of 8 paired GC and GC-associated non-neoplastic mucosae (GCN) using MethyLight technology and selected 27 DNA methylation markers showing higher methylation frequency or level in GC than in GCN. These markers were then analyzed in a tester set of 25 paired GC and GCN and 27 chronic gastritis (CG) from non-cancer patients to generate their DNA methylation profiles. We identified 17 novel methylation markers in GC, including SFRP4, SEZ6L, TWIST1, BCL2, KL, TERT, SCGB3A1, IGF2, GRIN2B, SFRP5, DLEC1, HOXA1, CYP1B1, SMAD9, MT1G, NR3C1, and HOXA10. Of the 27 selected CpG island loci, 23 were methylated in GC, GCN, and CG and the remainder four loci (DLEC1, CHFR, CYP1B1, and NR3C1) were only methylated in GC. We found that the number of methylated loci was significantly higher in GC than in GCN or CG and that Helicobacter pylori infection was strongly associated with aberrant CpG island hypermethylation in CG. Hypermethylation was more prevalent in Epstein-Barr virus (EBV)-positive GC than in EBV-negative GC and in diffuse-type GC than in intestinal-type GC. Through our large-scale screening of 170 CpG island loci, we found 17 new DNA methylation markers of GC, which may serve as useful markers that may identify a distinct subset of GC.

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“…The current study found CIMP-H in 22% of GCs using four MINT genes MINT1, MINT2, MINT25 and MINT31 . In other studies, CIMP was de ned by the DNA methylation status of tumor-related genes, rather than MINT genes [18][19][20] -methylguanine DNAmethyltransferase was linked to the responsiveness of brain tumors to alkylating agents. These positive relationships between the DNA methylation of cancer-related genes and therapeutic ef cacy might be implicated in the longer survival time of GC patients with CIMP-H. Our data shows that the survival time of GC patients with CIMP-H is likely to be longer than those with CIMP-L/CIMP-N GCs, but no statistical differences were observed in survival time among patients with different CIMP status.…”

Section: Discussionmentioning

confidence: 99%

CpG Island Methylator Phenotype in Primary Gastric Carcinoma

Tojo

Konishi

Yano

et al. 2013

Showa Univ J Med Sci

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: Gastric cancers GC with methylation of multiple CpG islands have a CpG island methylator phenotype CIMP and they can have different biological features. The aim of this study was to investigate the DNA methylation status of GCs and its association with their clinicopathological features. We evaluated the methylation status of four genes MINT1, MINT2, MINT25 and MINT31 in 105 primary GCs using bisul te-pyrosequencing analysis. We classi ed tumors as CIMPhigh CIMP-H , CIMP-low CIMP-L or CIMP-negative CIMP-N based on the methylation of MINT1, MINT2, MINT25, and MINT31. Overall, the prevalence of CIMP-H, CIMP-L and CIMP-N was 22% 23/105 , 52% 55/105 and 26% 27/105 , respectively. We observed a signi cant difference in tumor stage stages I-II vs. stages III-IV between CIMP-H and CIMP-N tumors P 0.0435 . No significant differences were observed in clinicopathological characteristics gender, age, location and tumor differentiation among the CIMP phenotypes. The prognoses of patients with a CIMP-H tumor is likely to be better than those with CIMP-L or CIMP-N tumors, but these differences are not statistically signi cant P 0.074 and P 0.200 . Our results suggest that CIMP may de ne a subgroup of GCs with distinct biological features.

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CpG Island M`ethylation Status in Gastric Carcinoma with and without Infection of Epstein-Barr Virus

Cited by 187 publications

References 23 publications

The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes

The presence of JC virus in gastric carcinomas correlates with patient's age, intestinal histological type and aberrant methylation of tumor suppressor genes

DNA methylation profiles of gastric carcinoma characterized by quantitative DNA methylation analysis

CpG Island Methylator Phenotype in Primary Gastric Carcinoma

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