Promoter hypermethylation of the Chfr gene in neoplastic and non-neoplastic gastric epithelia.
While chromosomal instability is a common feature of human solid tumours, no abnormalities in genes involved in the mitotic checkpoint have been identified. However, recently, Chfr (checkpoint with forkhead associated and ring finger), a mitotic stress checkpoint gene, has been reported to be inactivated due to promoter hypermethylation in several types of human malignancy. To clarify whether Chfr promoter hypermethylation is involved in gastric carcinogenesis, we investigated the promoter methylation status of the Chfr gene in gastric cancer cell lines and primary gastric cancers. Non-neoplastic gastric epithelia from cancer-bearing and noncancer-bearing stomachs were also examined for Chfr promoter hypermethylation to study its cancer specificity. Two of 10 gastric cancer cell lines (20%) showed Chfr promoter hypermethylation with resultant loss of expression, which could be restored by 5-aza-2' deoxycytidine treatment. Chfr promoter hypermethylation was present in 35% (25 of 71) of primary tumours and occurred at similar frequencies in early and advanced stages. As for non-neoplastic gastric epithelia, 1% (one of 91) from noncancer-bearing and 5% (four of 71) from cancer-bearing stomachs exhibited Chfr promoter hypermethylation. Thus, Chfr promoter hypermethylation is mostly cancer specific and frequently leads to chromosome instability in gastric cancer.
Honda
T
T
Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
Tamura
G
G
Waki
T
T
Kawata
S
S
Nishizuka
S
S
Motoyama
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D018797:Cell Cycle Proteins / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D043171:Chromosomal Instability; D019175:DNA Methylation; D004847:Epithelial Cells; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic; D013270:Stomach / Q000166:cytology; D013274:Stomach Neoplasms / Q000235:genetics* / Q000503:physiopathology; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases