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

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

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26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)789-797
Number of pages9
JournalOncogene
Volume21
Issue number5
DOIs
Publication statusPublished - 2002 Jan 1

Keywords

  • Demethylation
  • Hepatocellular carcinoma
  • Postoperative recurrence
  • Repetitive sequence
  • Restriction landmark genomic scanning

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Itano, O., Ueda, M., Kikuchi, K., Hashimoto, O., Hayatsu, S., Kawaguchi, M., Seki, H., Aiura, K., & Kitajima, M. (2002). Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences. Oncogene, 21(5), 789-797. https://doi.org/10.1038/sj.onc.1205124