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Distinct methylated profiles in Helicobacter pylori dependent and independent gastric MALT lymphomas
  1. Y Kaneko1,
  2. S Sakurai2,
  3. M Hironaka2,
  4. S Sato2,
  5. S Oguni2,
  6. Y Sakuma2,
  7. K Sato3,
  8. K Sugano3,
  9. K Saito2
  1. 1Departments of Pathology and Gastroenterology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi, Japan
  2. 2Department of Pathology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi, Japan
  3. 3Department of Gastroenterology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi, Japan
  1. Correspondence to:
    Dr S Sakurai, Department of Pathology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi, Japan;
    ssakurai{at}jichi.ac.jp

Abstract

Background: Gastric mucosa associated lymphoid tissue (MALT) lymphomas are clinically subdivided into Helicobacter pylori dependent and independent, according to H pylori infection and the therapeutic course. In previous reports it has been suggested that H pylori independent cases develop from H pylori dependent cases, and sometimes transform into high grade diffuse large B cell lymphomas (DLBCLs).

Methods: To better understand the pathogenesis of H pylori dependent and independent MALT lymphomas, we analysed the methylation profiles of eight independent CpG islands, including p15, p16, p73, hMLH1, death associated protein kinase, MINT1, MINT2, and MINT31 in H pylori dependent and independent MALT lymphomas, DLBCLs, and H pylori associated chronic gastritis.

Results: We first confirmed that H pylori independent cases had a high incidence of t(11;18)(q21;q21) (4/8 cases) and aberrant BCL10 expression (7/8 cases) compared with H pylori dependent cases and gastric DLBCLs. In the methylation pattern study, all 13 H pylori dependent MALT lymphomas had more than four methylated loci while H pylori independent cases had less than two. According to the previous criterion, all H pylori dependent MALT lymphomas (13/13, 100%) and five of 10 (50%) DLBCLs were classified as CpG island methylator phenotype positive (CIMP+). In contrast, all H pylori independent MALT lymphomas were CIMP−.

Conclusion: The distinct methylation pattern together with lack of chromosomal translocation in H pylori dependent MALT lymphomas suggest that H pylori dependent and independent MALT lymphomas have a different pathogenesis.

  • mucosa associated lymphoid tissue
  • Helicobacter pylori
  • methylation
  • lymphoma
  • MALT, mucosa associated lymphoid tissue
  • DLBCLs, diffuse large B cell lymphomas
  • CIMP, CpG island methylator phenotype
  • API2, apoptosis inhibitor 2
  • PCR, polymerase chain reaction
  • RT, reverse transcriptase
  • GAPDH, glyceraldehydes-3-phosphate dehydrogenase
  • MSP, methylation specific PCR
  • ROS, reactive oxygen species
  • DAP, death associated protein
  • MINT, methylated in tumours
  • hMLH, human Mut L homologue

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