High‐density methylation of p14ARF and p16INK4A in Epstein‐Barr virus–associated gastric carcinoma

Sakuma, Kazuya; Chong, Ja-Mun; Sudo, Makoto; Ushiku, Tetsuo; Inoue, Yoko; Shibahara, Junji; Uozaki, Hiroshi; Nagai, Hideo; Fukayama, Masashi

doi:10.1002/ijc.20420

Cited by 65 publications

(36 citation statements)

References 22 publications

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“…12,13 Both patterns of global hypomethylation and gene-specific hypermethylation have been reported in the host genome following EBV transformation. [14][15][16][17][18][19] It has also been suggested that epigenetic modifications in cell lines may result from intrinsic factors associated with cell culturing, 4,20 including altered methylation maintenance in response to the availability of methyl donors in the culturing media, 21 and altered methylation over time with increasing passage number. 22 The observed differences in methylation between PBLs and LCLs may also be explained by cell-type specific methylation.…”

Section: Resultsmentioning

confidence: 99%

Comparative analysis of DNA methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines

Brennan¹,

Ehrich²,

Brazil

et al. 2009

Epigenetics

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Previous reports have shown that DNA methylation profiles within primary human malignant tissues are altered when these cells are transformed into cancer cell lines. However, it is unclear if similar differences in DNA methylation profiles exist between DNA derived from peripheral blood leukocytes (PBLs) and corresponding Epstein-Barr Virus transformed lymphoblastoid cell lines (LCLs). To assess the utility of LCLs as a resource for methylation studies we have compared DNA methylation profiles in promoter and 5' regions of 318 genes in PBL and LCL sample pairs from patients with type 1 diabetes with or without nephropathy. We identified a total of 27 (~8%) genes that revealed different DNA methylation profiles in PBL compared with LCL-derived DNA samples. In conclusion, although the profiles for most promoter regions were similar between PBL-LCL pairs, our results indicate that LCL-derived DNA may not be suitable for DNA methylation studies at least in diabetic nephropathy.

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Section: Resultsmentioning

confidence: 99%

Comparative analysis of DNA methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines

Brennan¹,

Ehrich²,

Brazil

et al. 2009

Epigenetics

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“…Several studies have shown that methylation of the P16 gene was intimately associated with Epstein-Barr virus infection in gastric carcinomas. 42,43 Similarly, Goel et al 22 have reported an association between the presence of JCV in colorectal carcinomas and hypermethylation of several tumor-related genes including P16. Consistent with the aforementioned findings, in this study we found that hypermethylation of P16 and P14 were significantly correlated with JCV presence (P ¼ 0.007, P ¼ 0.003, respectively).…”

Section: Discussionmentioning

confidence: 96%

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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“…51 In GC, a relation between Epstein-Barr virus and DNA methylation has been reported. 52,53 DNA methylation occurs early in the multistep process of stomach carcinogenesis, 5,54 and CIMP is detected in some normal gastric mucosa. 13 Thus, DNA methylation may contribute to carcinogenesis but not progression.…”

Section: Discussionmentioning

confidence: 99%

Accumulation of DNA methylation is associated with tumor stage in gastric cancer

Oue

Mitani

Motoshita

et al. 2006

Cancer

129

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We present a methodological framework for estimating the degree of mixing between successive miscible fluids pumped along a near‐horizontal pipe. Either or both of the fluids can be non‐Newtonian, of Herschel–Bulkley type. Overall it is considered that the objective is to minimise mixing. In laminar regimes our estimates are based on front velocity of the leading displacement front. In turbulent regimes the spreading mechanism is dispersion. In addition to the estimates of mixing volumes/lengths, we also predict a minimal flow rate necessary in order to achieve a successful displacement of the residual fluid. © 2013 Canadian Society for Chemical Engineering

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High‐density methylation of p14^ARF and p16^INK4A in Epstein‐Barr virus–associated gastric carcinoma

Cited by 65 publications

References 22 publications

Comparative analysis of DNA methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines

Comparative analysis of DNA methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines

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

Accumulation of DNA methylation is associated with tumor stage in gastric cancer

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