Clustered DNA methylation changes in polycomb target genes in early-stage liver cancer

Yao Li Chen, Chih Jan Ko, Ping Yi Lin, Wan Ling Chuang, Chia Chen Hsu, Pei Yi Chu, Mei Yu Pai, Chun Chun Chang, Ming Han Kuo, Yi Ru Chu, Chun Hsin Tung, Tim H.M. Huang, Yu Wei Leu, Shu Huei Hsiao

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Polycomb-group proteins mark specific chromatin conformations in embryonic and somatic stem cells that are critical for maintenance of their "stemness" These proteins also mark altered chromatin modifications identified in various cancers. In normal differentiated cells or advanced cancerous cells, these polycomb-associated loci are frequently associated with increased DNA methylation. It has thus been hypothesized that changes in DNA methylation status within polycomb-associated loci may dictate cell fate and that abnormal methylation within these loci may be associated with tumor development. To assess this, we examined the methylation states of four polycomb target loci - Trip10, Casp8AP2, ENSA, and ZNF484 - in liver cancer. These four targets were selected because their methylation levels are increased during mesenchymal stem cell-to-liver differentiation. We found that these four loci were hypomethylated in most early-stage liver cancer specimens. For comparison, two non-polycomb tumor suppressor genes, HIC1 and RassF1A, were also examined. Whereas the methylation level of HIC1 did not differ significantly between normal and tumor samples, RassF1A was significantly hypermethylated in liver tumor samples. Unsupervised clustering analysis classified the methylation changes within polycomb and non-polycomb targets to be independent, indicating independent epigenetic evolution. Thus, pre-deposited polycomb marks within somatic stem cells may contribute to the determination of methylation changes during hepatic tumorigenesis.

Original languageEnglish (US)
Pages (from-to)290-296
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume425
Issue number2
DOIs
StatePublished - Aug 24 2012

Keywords

  • Chromatin immunoprecipitation
  • DNA methylation
  • Epigenetic
  • Liver cancer

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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