title: Checkpoint with forkhead-associated and ring finger promoter hypermethylation correlates with microsatellite instability in gastric cancer.
abstract: OBJECTIVE
  To examine the methylation status of the promoter region of the checkpoint with forkhead-associated and ring finger (CHFR) and microsatellite mutator status in 59 primary gastric cancers.
  
  
  METHODS
  We investigated the promoter methylation of CHFR in 59 cases of gastric cancer using methylation-specific PCR. Five microsatellite loci were analyzed using high-intensity microsatellite analysis reported previously, and p53 gene mutations were investigated by direct sequencing.
  
  
  RESULTS
  Twenty cases (33.9%) showed promoter methylation and no relation was observed with the clinicopathological factors. We found that the promoter methylation of CHFR was frequently accompanied with microsatellite instability (MIN). Seven of 20 (35.0%) cases showed MIN in hypermethylation of the CHFR tumor, while three of 39 (7.7%) cases showed MIN in the non-methylated CHFR tumor (P < 0.01). However, we failed to find any relationship between CHFR methylation and p53 mutation status.
  
  
  CONCLUSIONS
  The coordinated loss of both the mitotic check point function and mismatch repair system suggests the potential to overcome the cell cycle check point, which may lead to an accumulation of mutations. However, the p53 mutation was not related to hypermethylation of the CHFR promoter and MIN, which indicates that an abnormality in p53 occurs as an independent process from the mismatch repair deficiency in carcinogenesis.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. okieiji@surg2.med.kyushu-u.ac.jp
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Rintaro
authors.initials: R
authors.lastname: Yoshida
authors.forename: Takanobu
authors.initials: T
authors.lastname: Masuda
authors.forename: Koji
authors.initials: K
authors.lastname: Ando
authors.forename: Masahiiko
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Eriko
authors.initials: E
authors.lastname: Tokunaga
authors.forename: Masaru
authors.initials: M
authors.lastname: Morita
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kakeji
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D016159:Tumor Suppressor Protein p53; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases