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Hypomethylation of Alu repetitive elements in esophageal mucosa, and its potential contribution to the epigenetic field for cancerization

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Abstract

Background

Aberrant hypermethylation of specific genes is present in esophageal squamous cell carcinomas (ESCCs). Such hypermethylation is also present in normal-appearing esophageal mucosae of ESCC patients and is considered to contribute to the formation of a field for cancerization. On the other hand, the presence of global hypomethylation in ESCCs or in their background esophageal mucosae is unknown.

Method

We collected 184 samples of esophageal mucosae (95 normal mucosae from healthy subjects, and 89 non-cancerous background mucosae from ESCC patients) and 93 samples of ESCCs. Methylation levels of repetitive elements (Alu, LINE1) and cancer/testis antigen genes (NY-ESO-1, MAGE-C1) were measured by bisulfite pyrosequencing and quantitative methylation-specific PCR, respectively.

Results

Methylation levels of Alu, LINE1, NY-ESO-1, and MAGE-C1 were significantly lower in ESCCs than in their background and normal mucosae. Also, in the background mucosae, a significant decrease of the Alu methylation level compared with the normal mucosae was present. In ESCCs, methylation levels of the two repetitive elements and the two cancer/testis antigen genes were correlated with each other.

Conclusion

This is the first study to show the presence of global hypomethylation in ESCCs, and even in their non-cancerous background mucosae. Alu hypomethylation might reflect the severity of an epigenetic field for cancerization.

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Abbreviations

ALDH2:

Acetaldehyde dehydrogenase 2

LINE1:

Long interspersed nucleotide element 1

PCR:

Polymerase chain reaction

UICC:

Union for International Cancer Control

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Acknowledgments

This study was supported by Grants-in-Aid for the National Cancer Center Research and Development Fund, and by the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct) from the Ministry of Education, Culture, Science and Sport, Japan. Y. M. and K. G. are recipients of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Yasunori Matsuda, Satoshi Yamashita, Tohru Niwa, Takeichi Yoshida, Ken Gyobu & Toshikazu Ushijima

  2. Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Yasunori Matsuda, Shigeru Lee & Harushi Osugi

  3. Department of Internal Medicine, Collage of Medicine, National Taiwan University, Taipei, Taiwan

    Yi-Chia Lee & Ming-Shiang Wu

  4. Esophageal Surgery Division, National Cancer Center Hospital, Tokyo, Japan

    Hiroyasu Igaki

  5. Pathology of Clinical Laboratory Division, National Cancer Center Hospital, Tokyo, Japan

    Ryoji Kushima

  6. Department of Cardiovascular Surgery, Graduate School of Medicine, Osaka City University, Osaka, Japan

    Shigefumi Suehiro

Authors
  1. Yasunori Matsuda
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  2. Satoshi Yamashita
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  3. Yi-Chia Lee
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  5. Takeichi Yoshida
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  6. Ken Gyobu
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  12. Shigefumi Suehiro
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  13. Toshikazu Ushijima
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Corresponding author

Correspondence to Toshikazu Ushijima.

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Matsuda, Y., Yamashita, S., Lee, YC. et al. Hypomethylation of Alu repetitive elements in esophageal mucosa, and its potential contribution to the epigenetic field for cancerization. Cancer Causes Control 23, 865–873 (2012). https://doi.org/10.1007/s10552-012-9955-4

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  • DOI: https://doi.org/10.1007/s10552-012-9955-4

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