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Global DNA hypomethylation is an early event in Helicobacter pylori-related gastric carcinogenesis
  1. Debora Compare1,
  2. Alba Rocco1,
  3. Eleonora Liguori1,
  4. Francesco Paolo D'Armiento2,
  5. Giovanni Persico3,
  6. Stefania Masone3,
  7. Enrico Coppola-Bottazzi3,
  8. Renzo Suriani4,
  9. Marco Romano5,
  10. Gerardo Nardone1
  1. 1Department of Clinical and Experimental Medicine, Gastroenterology Unit, Federico II University of Naples, Naples, Italy
  2. 2Department of Morphological and Functional Science, Pathology Unit, Federico II University of Naples, Naples, Italy
  3. 3Department of Surgery and Advanced Technologies, Center of Excellence for Technical Innovation in Surgery (ITC), Federico II University of Naples, Naples, Italy
  4. 4Gastroenterologist Department of Gastroenterology, Ospedale degli Infermi, Rivoli, Italy
  5. 5Department of Clinical and Experimental Medicine, Gastroenterology Unit, Second University of Naples, Italy
  1. Correspondence to Gerardo Nardone, Associate Professor of Gastroenterology, Department of Clinical and Experimental Medicine, Gastroenterology Unit, University “Federico II” of Naples, Naples, Italy, Via S. Pansini 5, 80131 Naples, Italy; nardone{at}


Aim Cancer, particularly gastric cancer (GC), is prevalently an epigenetic phenomenon that is dependent on an altered DNA methylation pattern. In gastric carcinogenesis, many genes show aberrant methylation; however, none of them may be used as a biomarker of cancer risk and progression. The authors aimed to evaluate the global DNA methylation of gastric mucosa in Helicobacter pylori (Hp)-related chronic gastritis, in GC and in 10 patients with preneoplastic lesions (ie, atrophy and intestinal metaplasia) followed up for 10 years.

Methods The authors analysed 93 dyspeptic patients who underwent upper endoscopy, 41 surgical GC samples and 10 patients with preneoplastic gastric lesions followed up for 10 years after successful Hp eradication therapy. Global DNA methylation status and surrogate markers of cell proliferation and apoptosis were evaluated by immunohistochemistry using the anti-5-methylcytosine (5-MC), anti-Ki-67 and anti-p53 (anti-apoptotic marker)-specific antibodies, respectively.

Results Global DNA methylation of gastric mucosa gradually decreased from normal mucosa to Hp-positive gastritis, Hp-positive chronic atrophic gastritis, independent of Cag-A status and GC; however, the variation was significant (p<0.05) only between Hp-negative subjects and Hp-positive chronic gastritis. Interestingly, the 5-MC immunostaining was absent in areas of intestinal metaplasia. In the 10 patients with preneoplastic lesions, global DNA methylation decreased over time despite the eradication of Hp infection, but reached significance only at 10 years versus baseline. The 5-MC immunostaining negatively correlated with Ki-67 and p53 expression in all groups.

Conclusion Global DNA hypomethylation is an early molecular event in Hp-related gastric carcinogenesis. Further studies with more cases and a longer follow-up are needed to establish the potential GC predictive role of DNA hypomethylation.

  • DNA methylation
  • 5-methylcytosine
  • Helicobacter pylori
  • gastric cancer
  • gastric pathology
  • genetics
  • metaplasia

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  • DC, AR, MR and GN equally contributed to this study.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Institutional Ethics Committee of Federico II University of Naples.

  • Provenance and peer review Not commissioned; externally peer reviewed.