title: Identification of DNA methylation changes associated with human gastric cancer.
abstract: BACKGROUND
  Epigenetic alteration of gene expression is a common event in human cancer. DNA methylation is a well-known epigenetic process, but verifying the exact nature of epigenetic changes associated with cancer remains difficult.
  
  
  METHODS
  We profiled the methylome of human gastric cancer tissue at 50-bp resolution using a methylated DNA enrichment technique (methylated CpG island recovery assay) in combination with a genome analyzer and a new normalization algorithm.
  
  
  RESULTS
  We were able to gain a comprehensive view of promoters with various CpG densities, including CpG Islands (CGIs), transcript bodies, and various repeat classes. We found that gastric cancer was associated with hypermethylation of 5' CGIs and the 5'-end of coding exons as well as hypomethylation of repeat elements, such as short interspersed nuclear elements and the composite element SVA. Hypermethylation of 5' CGIs was significantly correlated with downregulation of associated genes, such as those in the HOX and histone gene families. We also discovered long-range epigenetic silencing (LRES) regions in gastric cancer tissue and identified several hypermethylated genes (MDM2, DYRK2, and LYZ) within these regions. The methylation status of CGIs and gene annotation elements in metastatic lymph nodes was intermediate between normal and cancerous tissue, indicating that methylation of specific genes is gradually increased in cancerous tissue.
  
  
  CONCLUSIONS
  Our findings will provide valuable data for future analysis of CpG methylation patterns, useful markers for the diagnosis of stomach cancer, as well as a new analysis method for clinical epigenomics investigations.
authors: Department of Biochemistry, College of Life Science and Technology, Yonsei University, Seoul, Korea.
authors: Jung-Hoon
authors: JH
authors: Park
authors: Jinah
authors: J
authors: Park
authors: Jung Kyoon
authors: JK
authors: Choi
authors: Jaemyun
authors: J
authors: Lyu
authors: Min-Gyun
authors: MG
authors: Bae
authors: Young-Gun
authors: YG
authors: Lee
authors: Jae-Bum
authors: JB
authors: Bae
authors: Dong Yoon
authors: DY
authors: Park
authors: Han-Kwang
authors: HK
authors: Yang
authors: Tae-You
authors: TY
authors: Kim
authors: Young-Joon
authors: YJ
authors: Kim
mesh_terms: D001681:Biological Assay; D002877:Chromosomes, Human / Q000235:genetics; D016000:Cluster Analysis; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005753:Gastric Mucosa / Q000378:metabolism; D020868:Gene Silencing; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D058977:Molecular Sequence Annotation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017422:Sequence Analysis, DNA; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D012333:RNA, Messenger