title: CpG methylation of transcription factor 4 in gastric carcinoma.
abstract: BACKGROUND
  Epigenetic silencing of tumor-related genes by CpG island methylation is an important mechanism for the development of many tumors, including gastric carcinoma. Deregulation of transcription factor 4 (TCF4) by promoter methylation was recently shown to play a key role in gastric carcinogenesis.
  
  
  METHODS
  The extent of methylation in the TCF4 promoter was assessed using methylation-specific polymerase chain reaction (MSP) and pyrosequencing (PS) in 120 gastric carcinoma (GC) samples collected during gastrectomy, and in 40 normal gastric mucosa samples.
  
  
  RESULTS
  The PS analysis of GCs revealed a higher frequency of TCF4 methylation (75.8%; 91/120). The methylation frequency for TCF4 by both MSP and PS techniques was significantly higher in advanced (75.0 and 91.7%, respectively) compared with early (60.0 and 60.0%, respectively, p < 0.05) GCs. There was a significant difference in TCF4 methylation between GCs and normal gastric mucosa (67.5 vs. 40.0%, respectively, by MSP and 75.8 vs. 30.0%, respectively, by PS; p < 0.05). There was significant correlation between TCF4 methylation status by PS and tumor size (p = 0.004), Lauren classification (p = 0.043), depth of invasion (p < 0.001), nodal metastasis (p = 0.021), and tumor-node-metastasis (TNM) stage (p = 0.045).
  
  
  CONCLUSIONS
  These results suggest that inactivation of TCF4 by promoter methylation may play a role in the early stage of gastric carcinoma progression. Furthermore, standard polymerase chain reaction followed by PS may provide a more specific and quantitative diagnostic alternative to MSP, which may be of benefit in oncology research.
authors.affiliation: Division of Gastroenterologic Surgery, Department of Surgery, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jae Kyoon
authors.initials: JK
authors.lastname: Joo
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Ho Gun
authors.initials: HG
authors.lastname: Kim
authors.forename: Dong Yi
authors.initials: DY
authors.lastname: Kim
authors.forename: Seong Yeob
authors.initials: SY
authors.lastname: Ryu
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Lee
authors.forename: Jae Hyuk
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors