title: Hypomethylation of Alu repetitive elements in esophageal mucosa, and its potential contribution to the epigenetic field for cancerization.
abstract: BACKGROUND
  Aberrant hypermethylation of specific genes is present in esophageal squamous cell carcinomas (ESCCs). Such hypermethylation is also present in normal-appearing esophageal mucosae of ESCC patients and is considered to contribute to the formation of a field for cancerization. On the other hand, the presence of global hypomethylation in ESCCs or in their background esophageal mucosae is unknown.
  
  
  METHODS
  We collected 184 samples of esophageal mucosae (95 normal mucosae from healthy subjects, and 89 non-cancerous background mucosae from ESCC patients) and 93 samples of ESCCs. Methylation levels of repetitive elements (Alu, LINE1) and cancer/testis antigen genes (NY-ESO-1, MAGE-C1) were measured by bisulfite pyrosequencing and quantitative methylation-specific PCR, respectively.
  
  
  RESULTS
  Methylation levels of Alu, LINE1, NY-ESO-1, and MAGE-C1 were significantly lower in ESCCs than in their background and normal mucosae. Also, in the background mucosae, a significant decrease of the Alu methylation level compared with the normal mucosae was present. In ESCCs, methylation levels of the two repetitive elements and the two cancer/testis antigen genes were correlated with each other.
  
  
  CONCLUSIONS
  This is the first study to show the presence of global hypomethylation in ESCCs, and even in their non-cancerous background mucosae. Alu hypomethylation might reflect the severity of an epigenetic field for cancerization.
authors.affiliation: Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Yi-Chia
authors.initials: YC
authors.lastname: Lee
authors.forename: Tohru
authors.initials: T
authors.lastname: Niwa
authors.forename: Takeichi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Ken
authors.initials: K
authors.lastname: Gyobu
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Igaki
authors.forename: Ryoji
authors.initials: R
authors.lastname: Kushima
authors.forename: Shigeru
authors.initials: S
authors.lastname: Lee
authors.forename: Ming-Shiang
authors.initials: MS
authors.lastname: Wu
authors.forename: Harushi
authors.initials: H
authors.lastname: Osugi
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Suehiro
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ushijima
mesh_terms: D020087:Alu Elements; D000951:Antigens, Neoplasm / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D057890:Epigenomics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D000951:Antigens, Neoplasm; C110905:MAGEC1 protein, human; C402404:NEMF protein, human; D009363:Neoplasm Proteins; D029543:Nucleocytoplasmic Transport Proteins