title: Clustered DNA methylation changes in polycomb target genes in early-stage liver cancer.
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.
authors: Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua, Taiwan.
authors: Yao-Li
authors: YL
authors: Chen
authors: Chih-Jan
authors: CJ
authors: Ko
authors: Ping-Yi
authors: PY
authors: Lin
authors: Wan-Ling
authors: WL
authors: Chuang
authors: Chia-Chen
authors: CC
authors: Hsu
authors: Pei-Yi
authors: PY
authors: Chu
authors: Mei-Yu
authors: MY
authors: Pai
authors: Chun-Chun
authors: CC
authors: Chang
authors: Ming-Han
authors: MH
authors: Kuo
authors: Yi-Ru
authors: YR
authors: Chu
authors: Chun-Hsin
authors: CH
authors: Tung
authors: Tim H-M
authors: TH
authors: Huang
authors: Yu-Wei
authors: YW
authors: Leu
authors: Shu-Huei
authors: SH
authors: Hsiao
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D056426:Genetic Loci / Q000235:genetics; D056945:Hep G2 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D063146:Polycomb-Group Proteins / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C485604:CASP8AP2 protein, human; D002135:Calcium-Binding Proteins; D002843:Chromatin; C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D063146:Polycomb-Group Proteins; C406285:TRIP10 protein, human