LINE-1 hypomethylation is associated with increased CpG island methylation in Helicobacter pylori-related enlarged-fold gastritis.
BACKGROUND
The molecular mechanism by which Helicobacter pylori infection leads to gastric cancer is not fully understood. Similarly, patients with enlarged-fold (EF+) gastritis, one cause of which is H. pylori infection, have an increased risk for gastric cancer, although again molecular mechanism is unclear. In the present study, we analyzed the methylation status of long interspersed nucleotide elements (LINE-1) and three cancer-related genes in a panel of gastric mucosae, with or without EF+ gastritis.


METHODS
We used bisulfite pyrosequencing to assess the levels of LINE-1, CDH1, CDH13, and PGP9.5 methylation in 78 gastric mucosa specimens from 48 patients.


RESULTS
Levels of LINE-1 methylation were significantly reduced in mucosae from patients with EF+ gastritis. This hypomethylation of LINE-1 was associated with increased methylation of the 5' CpG islands of the genes, which suggests that, in EF+ gastritis, the methylation of the promoter regions of certain genes is accompanied by global demethylation of repetitive sequences.


CONCLUSIONS
Our results indicate that genomewide hypomethylation and regional hypermethylation occur in EF+ gastritis and may contribute to the tumorigenesis of diffuse-type gastric cancers.
Yamamoto
Eiichiro
E
First Department of Internal Medicine, Sapporo Medical University, South 1,West 16, Chuo-ku, Sapporo 060-8543, Japan.
Toyota
Minoru
M
Suzuki
Hiromu
H
Kondo
Yutaka
Y
Sanomura
Tamana
T
Murayama
Yoko
Y
Ohe-Toyota
Mutsumi
M
Maruyama
Reo
R
Nojima
Masanori
M
Ashida
Masami
M
Fujii
Kyoko
K
Sasaki
Yasushi
Y
Hayashi
Norio
N
Mori
Mitsuru
M
Imai
Kohzoh
K
Tokino
Takashi
T
Shinomura
Yasuhisa
Y
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000235:genetics* / Q000382:microbiology; D016481:Helicobacter Infections / Q000235:genetics*; D016480:Helicobacter pylori; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology; D043222:Ubiquitin Thiolesterase / Q000235:genetics
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C099972:H-cadherin; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase