Relationship between LINE-1 hypomethylation and Helicobacter pylori infection in gastric mucosae

Keisuke Kosumi; Yoshifumi Baba; Takatsugu Ishimoto; Kazuto Harada; Keisuke Miyake; Daisuke Izumi; Ryuma Tokunaga; Asuka Murata; Kojiro Eto; Hidetaka Sugihara; Hironobu Shigaki; Shiro Iwagami; Yasuo Sakamoto; Yuji Miyamoto; Naoya Yoshida; Masayuki Watanabe; Yoshihiro Komohara; Motohiro Takeya; Hideo Baba

doi:10.1007/s12032-015-0571-5

Relationship between LINE-1 hypomethylation and Helicobacter pylori infection in gastric mucosae

Keisuke Kosumi, Yoshifumi Baba, Takatsugu Ishimoto, Kazuto Harada, Keisuke Miyake, Daisuke Izumi, Ryuma Tokunaga, Asuka Murata, Kojiro Eto, Hidetaka Sugihara, Hironobu Shigaki, Shiro Iwagami, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Yoshihiro Komohara, Motohiro Takeya, Hideo Baba

Cancer Prevention Training Program

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

The DNA methylation alterations occurring in human cancers have two types: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Recently, to assess global DNA methylation, long interspersed nucleotide element 1 (LINE-1) retrotransposons, constituting a substantial portion of the human genome, attracts much attention. The aim of the current study was to clarify the significance of LINE-1 methylation level for epigenetic field defects and the relationships among LINE-1 methylation level in gastric mucosae, clinical and pathological features, including infection by Helicobacter pylori (H. pylori), a bacterium implicated in gastric cancer. By bisulfite-PCR pyrosequencing, we quantified the LINE-1 methylation levels in noncancerous gastric mucosae and cancer tissues from 87 gastric cancer patients, in gastric mucosae from 17 autopsied individuals without gastric cancers and in 20 gastric fresh frozen samples from non-gastric cancer patients. LINE-1 methylation in the noncancerous gastric mucosae of gastric cancer patients was significantly higher than in cancer tissues (P = 0.0006), but significantly lower than in the gastric mucosae of the autopsied individuals (P = 0.026), suggesting the formation of epigenetic field defect in noncancerous gastric mucosae. Moreover, LINE-1 hypomethylation of noncancerous gastric mucosae in gastric cancer patients significantly correlated with H. pylori infection (P = 0.037). We prospectively confirmed the similar result in 20 non-gastric cancer patients (P = 0.010). LINE-1 hypomethylation of gastric mucosae significantly correlated with H. pylori infection, supporting the potential of LINE-1 methylation level as a surrogate marker of epigenetic field defects for gastric cancer cancerization, particularly induced by H. pylori.

Original language	English (US)
Journal	Medical Oncology
Volume	32
Issue number	4
DOIs	https://doi.org/10.1007/s12032-015-0571-5
State	Published - Apr 2015

Keywords

Epigenetic field defect
Gastric mucosae
Hypomethylation
Infection of Helicobacter pylori
LINE-1

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

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10.1007/s12032-015-0571-5

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Kosumi, K., Baba, Y., Ishimoto, T., Harada, K., Miyake, K., Izumi, D., Tokunaga, R., Murata, A., Eto, K., Sugihara, H., Shigaki, H., Iwagami, S., Sakamoto, Y., Miyamoto, Y., Yoshida, N., Watanabe, M., Komohara, Y., Takeya, M., & Baba, H. (2015). Relationship between LINE-1 hypomethylation and Helicobacter pylori infection in gastric mucosae. Medical Oncology, 32(4). https://doi.org/10.1007/s12032-015-0571-5

Kosumi, K, Baba, Y, Ishimoto, T, Harada, K, Miyake, K, Izumi, D, Tokunaga, R, Murata, A, Eto, K, Sugihara, H, Shigaki, H, Iwagami, S, Sakamoto, Y, Miyamoto, Y, Yoshida, N, Watanabe, M, Komohara, Y, Takeya, M & Baba, H 2015, 'Relationship between LINE-1 hypomethylation and Helicobacter pylori infection in gastric mucosae', Medical Oncology, vol. 32, no. 4. https://doi.org/10.1007/s12032-015-0571-5

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abstract = "The DNA methylation alterations occurring in human cancers have two types: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Recently, to assess global DNA methylation, long interspersed nucleotide element 1 (LINE-1) retrotransposons, constituting a substantial portion of the human genome, attracts much attention. The aim of the current study was to clarify the significance of LINE-1 methylation level for epigenetic field defects and the relationships among LINE-1 methylation level in gastric mucosae, clinical and pathological features, including infection by Helicobacter pylori (H. pylori), a bacterium implicated in gastric cancer. By bisulfite-PCR pyrosequencing, we quantified the LINE-1 methylation levels in noncancerous gastric mucosae and cancer tissues from 87 gastric cancer patients, in gastric mucosae from 17 autopsied individuals without gastric cancers and in 20 gastric fresh frozen samples from non-gastric cancer patients. LINE-1 methylation in the noncancerous gastric mucosae of gastric cancer patients was significantly higher than in cancer tissues (P = 0.0006), but significantly lower than in the gastric mucosae of the autopsied individuals (P = 0.026), suggesting the formation of epigenetic field defect in noncancerous gastric mucosae. Moreover, LINE-1 hypomethylation of noncancerous gastric mucosae in gastric cancer patients significantly correlated with H. pylori infection (P = 0.037). We prospectively confirmed the similar result in 20 non-gastric cancer patients (P = 0.010). LINE-1 hypomethylation of gastric mucosae significantly correlated with H. pylori infection, supporting the potential of LINE-1 methylation level as a surrogate marker of epigenetic field defects for gastric cancer cancerization, particularly induced by H. pylori.",

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author = "Keisuke Kosumi and Yoshifumi Baba and Takatsugu Ishimoto and Kazuto Harada and Keisuke Miyake and Daisuke Izumi and Ryuma Tokunaga and Asuka Murata and Kojiro Eto and Hidetaka Sugihara and Hironobu Shigaki and Shiro Iwagami and Yasuo Sakamoto and Yuji Miyamoto and Naoya Yoshida and Masayuki Watanabe and Yoshihiro Komohara and Motohiro Takeya and Hideo Baba",

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AU - Harada, Kazuto

AU - Miyake, Keisuke

AU - Izumi, Daisuke

AU - Tokunaga, Ryuma

AU - Murata, Asuka

AU - Eto, Kojiro

AU - Sugihara, Hidetaka

AU - Shigaki, Hironobu

AU - Iwagami, Shiro

AU - Sakamoto, Yasuo

AU - Miyamoto, Yuji

AU - Yoshida, Naoya

AU - Watanabe, Masayuki

AU - Komohara, Yoshihiro

AU - Takeya, Motohiro

AU - Baba, Hideo

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AB - The DNA methylation alterations occurring in human cancers have two types: global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Recently, to assess global DNA methylation, long interspersed nucleotide element 1 (LINE-1) retrotransposons, constituting a substantial portion of the human genome, attracts much attention. The aim of the current study was to clarify the significance of LINE-1 methylation level for epigenetic field defects and the relationships among LINE-1 methylation level in gastric mucosae, clinical and pathological features, including infection by Helicobacter pylori (H. pylori), a bacterium implicated in gastric cancer. By bisulfite-PCR pyrosequencing, we quantified the LINE-1 methylation levels in noncancerous gastric mucosae and cancer tissues from 87 gastric cancer patients, in gastric mucosae from 17 autopsied individuals without gastric cancers and in 20 gastric fresh frozen samples from non-gastric cancer patients. LINE-1 methylation in the noncancerous gastric mucosae of gastric cancer patients was significantly higher than in cancer tissues (P = 0.0006), but significantly lower than in the gastric mucosae of the autopsied individuals (P = 0.026), suggesting the formation of epigenetic field defect in noncancerous gastric mucosae. Moreover, LINE-1 hypomethylation of noncancerous gastric mucosae in gastric cancer patients significantly correlated with H. pylori infection (P = 0.037). We prospectively confirmed the similar result in 20 non-gastric cancer patients (P = 0.010). LINE-1 hypomethylation of gastric mucosae significantly correlated with H. pylori infection, supporting the potential of LINE-1 methylation level as a surrogate marker of epigenetic field defects for gastric cancer cancerization, particularly induced by H. pylori.

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Relationship between LINE-1 hypomethylation and Helicobacter pylori infection in gastric mucosae

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