Distinct methylated profiles in Helicobacter pylori dependent and independent gastric MALT lymphomas.
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-.


CONCLUSIONS
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.
Kaneko
Y
Y
Department of Pathology, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi, Japan.
Sakurai
S
S
Hironaka
M
M
Sato
S
S
Oguni
S
S
Sakuma
Y
Y
Sato
K
K
Sugano
K
K
Saito
K
K
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002352:Carrier Proteins; D002908:Chronic Disease; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D064550:Death-Associated Protein Kinases; D005260:Female; D005756:Gastritis / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins; D010641:Phenotype; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D014178:Translocation, Genetic
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000070957:MutL Protein Homolog 1