Aberrant DNA methylation on chromosome 16 is an early event in hepatocarinogenesis

Yae Kanai, S. Ushijima, H. Tsuda, Michiie Sakamoto, T. Sugimura, S. Hirohashi

Research output: Contribution to journalArticle

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Abstract

In order to clarify the significance of DNA methylation in both earlier and later stages of hepatocarcinogenesis, the DNA methylation state on chromosome 16, on which loss of heterozygosity (LOH) has frequently been detected in human hepatocellular carcinomas (HCCs), was examined. DNA from primary HCCs and tissues showing chronic hepatitis and liver cirrhosis, which are considered to be precancerous conditions, was analyzed by digestion with methylation-sensitive and non-sensitive restriction enzymes. DNA hypermethylation at the D16S32, tyrosine aminotransferase (TAT) and D16S7 loci and hypomethylation at the D16S4 locus were detected in 18%, 58%, 20% and 48% of examined HCCs, respectively. Aberrant DNA methylation occurred more frequently in advanced HCCs than in early HCCs. Moreover, DNA hypermethylation at the D16S32, TAT and D16S7 loci was frequently observed in chronic hepatitis and liver cirrhosis. The incidence of DNA hypermethylation was higher than that of LOH (42% at the TAT locus). These data suggest that DNA hypermethylation might predispose the locus to allelic loss. Aberrant DNA methylation is a significant change which may participate in the early developmental stages of HCCs.

Original languageEnglish
Pages (from-to)1210-1217
Number of pages8
JournalJapanese Journal of Cancer Research
Volume87
Issue number12
Publication statusPublished - 1996
Externally publishedYes

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Chromosomes, Human, Pair 16
DNA Methylation
Hepatocellular Carcinoma
Tyrosine Transaminase
Loss of Heterozygosity
DNA
Chronic Hepatitis
Liver Cirrhosis
Precancerous Conditions
Methylation
Digestion
Incidence
Enzymes

Keywords

  • Hepatocellular carcinoma
  • Loss of heterozygosity
  • Multistage carcinogenesis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Aberrant DNA methylation on chromosome 16 is an early event in hepatocarinogenesis. / Kanai, Yae; Ushijima, S.; Tsuda, H.; Sakamoto, Michiie; Sugimura, T.; Hirohashi, S.

In: Japanese Journal of Cancer Research, Vol. 87, No. 12, 1996, p. 1210-1217.

Research output: Contribution to journalArticle

Kanai, Y, Ushijima, S, Tsuda, H, Sakamoto, M, Sugimura, T & Hirohashi, S 1996, 'Aberrant DNA methylation on chromosome 16 is an early event in hepatocarinogenesis', Japanese Journal of Cancer Research, vol. 87, no. 12, pp. 1210-1217.
Kanai, Yae ; Ushijima, S. ; Tsuda, H. ; Sakamoto, Michiie ; Sugimura, T. ; Hirohashi, S. / Aberrant DNA methylation on chromosome 16 is an early event in hepatocarinogenesis. In: Japanese Journal of Cancer Research. 1996 ; Vol. 87, No. 12. pp. 1210-1217.
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AU - Hirohashi, S.

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AB - In order to clarify the significance of DNA methylation in both earlier and later stages of hepatocarcinogenesis, the DNA methylation state on chromosome 16, on which loss of heterozygosity (LOH) has frequently been detected in human hepatocellular carcinomas (HCCs), was examined. DNA from primary HCCs and tissues showing chronic hepatitis and liver cirrhosis, which are considered to be precancerous conditions, was analyzed by digestion with methylation-sensitive and non-sensitive restriction enzymes. DNA hypermethylation at the D16S32, tyrosine aminotransferase (TAT) and D16S7 loci and hypomethylation at the D16S4 locus were detected in 18%, 58%, 20% and 48% of examined HCCs, respectively. Aberrant DNA methylation occurred more frequently in advanced HCCs than in early HCCs. Moreover, DNA hypermethylation at the D16S32, TAT and D16S7 loci was frequently observed in chronic hepatitis and liver cirrhosis. The incidence of DNA hypermethylation was higher than that of LOH (42% at the TAT locus). These data suggest that DNA hypermethylation might predispose the locus to allelic loss. Aberrant DNA methylation is a significant change which may participate in the early developmental stages of HCCs.

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