Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma

Eri Arai, Saori Ushijima, Masahiro Gotoh, Hidenori Ojima, Tomoo Kosuge, Fumie Hosoda, Tatsuhiro Shibata, Tadashi Kondo, Sana Yokoi, Issei Imoto, Johji Inazawa, Setsuo Hirohashi, Yae Kanai

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

To clarify genome-wide DNA methylation profiles during hepatocarcinogenesis, bacterial artificial chromosome (BAC) array-based methylated CpG island amplification was performed on 126 tissue samples. The average numbers of BAC clones showing DNA hypo- or hypermethylation increased from noncancerous liver tissue obtained from patients with hepatocellular carcinomas (HCCs) (N) to HCCs. N appeared to be at the precancerous stage, showing DNA methylation alterations that were correlated with the future development of HCC. Using Wilcoxon test, 25 BAC clones, whose DNA methylation status was inherited by HCCs from N and were able to discriminate 15 N samples from 10 samples of normal liver tissue obtained from patients without HCCs (C) with 100% sensitivity and specificity, were identified. The criteria using the 25 BAC clones were able to discriminate 24 additional N samples from 26 C samples in the validation set with 95.8% sensitivity and 96.2% specificity. Using Wilcoxon test, 41 BAC clones, whose DNA methylation status was able to discriminate patients who survived more than 4 years after hepatectomy from patients who suffered recurrence within 6 months and died within a year after hepatectomy, were identified. The DNA methylation status of the 41 BAC clones was correlated with the cancer-free and overall survival rates of patients with HCC. Multivariate analysis revealed that satisfying the criteria using the 41 BAC clones was an independent predictor of overall outcome. Genome-wide alterations of DNA methylation may participate in hepatocarcinogenesis from the precancerous stage, and DNA methylation profiling may provide optimal indicators for carcinogenetic risk estimation and prognostication.

Original languageEnglish
Pages (from-to)2854-2862
Number of pages9
JournalInternational Journal of Cancer
Volume125
Issue number12
DOIs
Publication statusPublished - 2009 Dec 15
Externally publishedYes

Fingerprint

Bacterial Artificial Chromosomes
DNA Methylation
Hepatocellular Carcinoma
Genome
Clone Cells
Liver
Hepatectomy
Sensitivity and Specificity
CpG Islands
DNA Fingerprinting
Multivariate Analysis
Survival Rate
Recurrence
DNA

Keywords

  • Bacterial artificial chromosome array-based methylated CpG island amplification
  • Hepatocellular carcinoma
  • Multistage carcinogenesis
  • Precancerous condition
  • Prognostication

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma. / Arai, Eri; Ushijima, Saori; Gotoh, Masahiro; Ojima, Hidenori; Kosuge, Tomoo; Hosoda, Fumie; Shibata, Tatsuhiro; Kondo, Tadashi; Yokoi, Sana; Imoto, Issei; Inazawa, Johji; Hirohashi, Setsuo; Kanai, Yae.

In: International Journal of Cancer, Vol. 125, No. 12, 15.12.2009, p. 2854-2862.

Research output: Contribution to journalArticle

Arai, E, Ushijima, S, Gotoh, M, Ojima, H, Kosuge, T, Hosoda, F, Shibata, T, Kondo, T, Yokoi, S, Imoto, I, Inazawa, J, Hirohashi, S & Kanai, Y 2009, 'Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma', International Journal of Cancer, vol. 125, no. 12, pp. 2854-2862. https://doi.org/10.1002/ijc.24708
Arai, Eri ; Ushijima, Saori ; Gotoh, Masahiro ; Ojima, Hidenori ; Kosuge, Tomoo ; Hosoda, Fumie ; Shibata, Tatsuhiro ; Kondo, Tadashi ; Yokoi, Sana ; Imoto, Issei ; Inazawa, Johji ; Hirohashi, Setsuo ; Kanai, Yae. / Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma. In: International Journal of Cancer. 2009 ; Vol. 125, No. 12. pp. 2854-2862.
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