Methylation of <b>
                     <i>p16</i>
                  </b> CpG Islands Associated with Malignant Transformation of Gastric Dysplasia in a Population-Based Study

Sun, Yu; Deng, Dajun; You, Wei‐Cheng; Bai, Hua; Zhou, Jing; Shen, Lin; Ma, Junling; Xie, Yanbo; Li, Jiyou

doi:10.1158/1078-0432.ccr-03-0622

Cited by 75 publications

(63 citation statements)

References 28 publications

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“…Epigenetic silencing of a tumor suppressor gene could be the rate-limiting step that initiates the series of events leading to an invasive malignant tumor. Methylation of p16 gene appears to be a promising candidate to serve this purpose as shown in our study [81] and supported in a populationbased study by Sun et al that aberrant methylation of p16 promoter CpG islands might be useful to predict the malignant potential of dysplasia identified specifically in gastric biopsies [87].…”

Section: Discussionsupporting

confidence: 82%

Epigenetic alterations in gastric carcinogenesis

Choi

2005

Cell Res

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Gastric cancer is believed to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumor suppressor loss. Epigenetic alterations as a distinct and crucial mechanism to silence a variety of methylated tissue-specific and imprinted genes, have been extensively studied in gastric carcinoma and play important roles in gastric carcinogenesis. This review will briefly discuss the basic aspects of DNA methylation and CpG island methylation, in particular the epigenetic alterations of certain critical genes implicated in gastric carcinogenesis and its relevance of clinical implications.

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Section: Discussionsupporting

confidence: 82%

Epigenetic alterations in gastric carcinogenesis

Choi

2005

Cell Res

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“…Epithelial dysplasia is the main precancerous lesion in many organs in the body. We have proven that methylation of p16, the G1→S conversion checkpoint gene in the cell cycle, is a powerful biomarker for predicting malignant transformation of epithelial dysplasia [5,6]. This has been consistently confirmed by a number of independent studies in different countries [7][8][9].…”

Section: Differentiation and Adaptation Epigenetic Modificationsmentioning

confidence: 52%

Differentiation and adaptation epigenetic networks: Translational research in gastric carcinogenesis

Deng

2012

Chin. Sci. Bull.

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There are several kinds of epigenetic networks in the human body including the cell differentiation epigenetic network (DiEN) and the host adaptation epigenetic network (AdEN). DiEN networks are static and cell/tissue-specific. AdEN networks are variable and dependent upon environmental factors. DiEN and AdEN alterations can respectively serve as biomarkers for different kinds of diseases. Cancer is a consequence of accumulated pathophysiological adaptations of tissue stem cells to exposure of environmental carcinogens. Cancer cells are de-differentiated cells that obtain the capacity of unrestricted proliferation, local invasion, and distant migration/metastasis. Both DiEN and AdEN changes can be observed in cancer tissues. Alterations of DNA methylation are the most stable epigenetic modifications and can be sensitively detected in a small cell population. These advantages make DNA methylation the optimal biomarkers for detection of initiated cells in precancerous lesions and metastasis stem cells in cancer tissues. It has been proven that p16 methylation can be used as a diagnostic biomarker to determine malignant potential of epithelium dysplasia in many organs including the stomach. In a large-scale validation study on the DNA methylome of gastric carcinomas (GC), the methylation status of more than 90 CpG islands has been analyzed by DHPLC. Furthermore, GFRA1 demethylation and methylation of SRF and ZNF382 are frequent events during gastric carcinogenesis and consistently correlate to GC metastasis and overall survival of GC patients from China, Japan, and Korea, respectively. In a population study, it has been demonstrated that gradual increasing of plasma miR-211 and other miRNA levels may be an early risk predictor for GC development.

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“…High molecular weight genomic DNA was isolated and treated with bisulfite as reported previously (29). After being deparaffinized and rehydrated, biopsy tissues were digested by lysis buffer containing proteinase K at 50 C overnight and then modified with sodium bisulfite.…”

Section: Dna Extraction and Bisulfite Treatmentmentioning

confidence: 99%

Alterations of Cyclooxygenase-2 Methylation Levels Before and After Intervention Trial to Prevent Gastric Cancer in a Chinese Population

Zhang

Zeng

Nie

et al. 2016

Cancer Prevention Research

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To explore the epigenetic mechanisms underlying the effects of anti-Helicobacter pylori (H. pylori) alone and combined with COX-2 inhibitor (celecoxib), we dynamically evaluated the associations between COX-2 methylation alterations and gastric lesion evolution during the process of interventions. In a total of 809 trial participants COX-2 methylation levels were quantitatively detected before and after treatment. The self-comparison at the same stomach site for each subject showed significant methylation alteration differences among intervention groups (P < 0.001). With placebo group as reference, COX-2 methylation levels were decreased in anti-H. pylori [OR, 3.30; 95% confidence interval (CI), 2.16-5.02], celecoxib (OR, 2.04; 95% CI, 1.36-3.07), and anti-H. pylori followed by celecoxib (OR, 2.10; 95% CI, 1.38-3.17) groups. When stratified by baseline histology, the three active arms significantly decreased COX-2 methylation levels in indefinite dysplasia/dysplasia subjects, and ORs were 3.65 (95% CI, 1.96-6.80) for anti-H. pylori, 2.43 (95% CI 1.34-4.39) for celecoxib, and 2.80 (95% CI, 1.52-5.15) for anti-H. pylori followed by celecoxib, respectively. No additive effect on COX-2 methylation was found for anti-H. pylori followed by celecoxib than two treatments alone. Compared with subjects without methylation reduction, higher opportunity for gastric lesion regression was found in subjects with decreased COX-2 methylation levels, especially for indefinite dysplasia/dysplasia subjects (OR, 1.92; 95% CI, 1.03-3.60). These findings suggest that anti-H. pylori or celecoxib treatment alone could decrease COX-2 methylation levels in gastric mucosa. COX-2 methylation alteration was associated with the regression of indefinite dysplasia/dysplasia, which might serve as a potential biomarker for chemoprevention efficacy. Cancer Prev Res; 9(6); 484-90. Ó2016 AACR.

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Methylation of p16 CpG Islands Associated with Malignant Transformation of Gastric Dysplasia in a Population-Based Study

Cited by 75 publications

References 28 publications

Epigenetic alterations in gastric carcinogenesis

Epigenetic alterations in gastric carcinogenesis

Differentiation and adaptation epigenetic networks: Translational research in gastric carcinogenesis

Alterations of Cyclooxygenase-2 Methylation Levels Before and After Intervention Trial to Prevent Gastric Cancer in a Chinese Population

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