title: Methylation of the Tumor Suppressor Genes HIC1 and RassF1A Clusters Independently From the Methylation of Polycomb Target Genes in Colon Cancer.
abstract: BACKGROUND
  Methylation changes within tumor suppressor (TS) genes or polycomb group target (PcG) genes alter cell fates. Chromatin associated with PcG targets is bivalent in stem cells, while TS genes are not normally bivalent. PcG target methylation changes have been identified in tumor stem cells, and abnormal methylation is found in TS genes in cancers. If the epigenetic states of genes influence DNA methylation, then methylation of PcG targets and TS genes may evolve differently during cancer development. More importantly, methylation changes may be part of a sequence in tumorigenesis.
  
  
  METHODS
  Chromatin and methylation states of 4 PcG targets and 2 TS genes were determined in colon cancer cells. The methylation states were also detected in 100 pairs of colon cancer samples. Principle component analysis (PCA) was used to reveal whether TS methylation or PcG methylation was the main methylation change associated with colon cancers.
  
  
  RESULTS
  Chromatin and methylation states differ in colon cancer cell lines. The methylation states within PcG targets clustered independently from the methylation states in TS genes, a finding we previously reported in liver cancers. PCA in colon cancers revealed the strongest association with methylation changes in 2 TS genes, HIC1 and RassF1A. Loss of HIC1 methylation correlated with decreased tumor migration.
  
  
  CONCLUSIONS
  PcG and TS methylation states cluster independently from each other. The deduced principle component correlated better with TS methylation than PcG methylation in colon cancer. Abnormal methylation changes may represent a sequential biomarker profile to identify developing colon cancer.
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Hong-Chang
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Division of Colorectal Surgery, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Hsuan-Yuan
authors.initials: HY
authors.lastname: Huang
authors.affiliation: Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua, Taiwan.|School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yao-Li
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Chang Gung University College of Medicine, Taoyuan, Taiwan.|Chang Gung Institute of Technology, Taoyuan, Taiwan.
authors.forename: Kuan-Der
authors.initials: KD
authors.lastname: Lee
authors.affiliation: Department of Hematology and Oncology, Chang Gung Memorial Hospital, Chiayi, Chang Gung University College of Medicine, Taoyuan, Taiwan.|Chang Gung Institute of Technology, Taoyuan, Taiwan.|Department of Life Science, Human Epigenomics Center, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chia-Yi, Taiwan.
authors.forename: Yi-Ru
authors.initials: YR
authors.lastname: Chu
authors.affiliation: Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Ping-Yi
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Department of Life Science, Human Epigenomics Center, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chia-Yi, Taiwan.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Hsu
authors.affiliation: Department of Pathology, Show Chwan Memorial Hospital, Changhua, Taiwan.
authors.forename: Pei-Yi
authors.initials: PY
authors.lastname: Chu
authors.affiliation: Department of Molecular Medicine and Institute of Biotechnology, School of Medicine, Cancer Therapy and Research Center, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Tim H-M
authors.initials: TH
authors.lastname: Huang
authors.affiliation: Department of Life Science, Human Epigenomics Center, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chia-Yi, Taiwan.
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Hsiao
authors.affiliation: Department of Life Science, Human Epigenomics Center, Institute of Molecular Biology and Institute of Biomedical Science, National Chung Cheng University, Chia-Yi, Taiwan. bioywl@ccu.edu.tw.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Leu
mesh_terms: D002465:Cell Movement; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D063146:Polycomb-Group Proteins / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; D063146:Polycomb-Group Proteins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins