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Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences

Oncogene volume 21, pages 789–797 (2002)Cite this article

Abstract

Restriction landmark genomic scanning (RLGS) was utilized to identify novel genomic alterations in hepatocellular carcinoma (HCC). Thirty-one HCC samples were examined by RLGS. Two high intensity spots were common to several RLGS profiles of different HCCs. Nucleotide sequencing and homology search analysis showed that these spots represented repetitive sequences, Human tandem repeat sequence (Genbank, L09552) and centromeric NotI cluster (Genbank, Y10752). These intensified signals were attributable to the occurrence of demethylated areas in the recognition sequence of the NotI site of the corresponding fragments. The intensity of these spots in the RLGS profile reflects their degree of demethylation, which was significantly correlated with postoperative recurrence, even in patients regarded as belonging to the good prognosis group by conventional prognostic factors. Multivariate analysis showed that the intensities of the two spots retained independent prognostic value. This is a new type of predictive factor for HCC based on epigenetic changes in hepatocarcinogenesis, and in the future it is expected to be of great value in making preoperative diagnosis and selecting postoperative therapy.

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Acknowledgements

The authors would like to thank T Muramatsu and Y Inaba for their expert technical assistance and N Sugimoto (Sanwa Kagaku Kenkyusho Co Ltd) for his valuable advice on statistical analysis. This work was supported by the a Grant-in-Aid from the Ministry of Education, Science and Culture and the Ministry of Health and Welfare of Japan and by a National Grant-in-Aid for the Establishment of a High-Tech Research Center in a Private Japanese University.

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Authors and Affiliations

  1. Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Osamu Itano, Masakazu Ueda, Osamu Hashimoto, Shigeo Hayatsu, Masaharu Kawaguchi, Hiroaki Seki, Kouichi Aiura & Masaki Kitajima

  2. Department of Surgery, Tokyo Denryoku Hospital, 9-2 Shinanomachi, Shinjuku-ku, Tokyo, 160-0016, Japan

    Kiyoshi Kikuchi

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Itano, O., Ueda, M., Kikuchi, K. et al. Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences. Oncogene 21, 789–797 (2002). https://doi.org/10.1038/sj.onc.1205124

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