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Japanese Journal of Clinical Oncology 30:306-309 (2000)
© 2000 Foundation for Promotion of Cancer Research

Hypomethylation of LINE1 Retrotransposon in Human Hepatocellular Carcinomas, but Not in Surrounding Liver Cirrhosis

Daiya Takai1, Yukiko Yagi1, Nagy Habib2, Takashi Sugimura1 and Toshikazu Ushijima1,+

1Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan and 2Department of Surgery, Hammersmith Hospital, Royal Postgraduate Medical School, London, UK

Background: Cytosine methylation of LINE1 (L1) elements, some of which are capable of retrotransposition in human cells, is known to play important roles in transcriptional repression of these retrotransposons. We have previously identified consistent hypomethylation of L1 elements in mouse liver tumors by a genome-wide search technique for aberrant methylations. In this study, we analyzed the methylation status of the L1 elements in human hepatocellular carcinomas (HCCs).

Methods: Nine pairs of an HCC and its surrounding tissue were obtained from clinical cases. Genomic DNA was digested with HpaII, a methylation-sensitive restriction enzyme, and hybridi­zed with a probe derived from the promoter region of the L1 elements.

Results: Hypomethylation of the L1 elements was detected in eight of the nine HCCs, but never in the surrounding liver tissues, whether or not liver cirrhosis was present.

Conclusion: Specific occurrence of the hypomethylation of the L1 elements in the HCCs indicated its diagnostic value for malignancy. The hypomethylation could also lead to increased incidence of retrotransposition and resultant genomic instability in HCCs.

+ For reprints and all correspondence: Toshikazu Ushijima, Carcinogenesis Division, National Cancer Center Research Institute, 1–1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. E-mail: tushijim@ncc.go.jp


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