Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers.
The CHFR gene, which was recently cloned by Scolnick and Halazonetis in search for a novel mitotic checkpoint gene with fork-head association motifs, has been suggested to play a key role in the mitotic prophase checkpoint. In this study, we demonstrated tumor-specific aberrant hypermethylation of the promoter region of the CHFR gene in a significant fraction of lung cancers in association with loss of detectable levels of CHFR transcripts. Aberrant hypermethylation was observed in seven of 37 primary lung cancer cases. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored expression of the CHFR gene in lung cancer cell lines exhibiting aberrant hypermethylation and loss of its expression. In contrast, genetic alterations were found to be infrequent in lung cancers. This is the first description of aberrant hypermethylation of the CHFR gene in any type of human cancer, and provides further evidence of the involvement of multiple checkpoint alterations in lung cancer.
Mizuno
Kotaro
K
Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
Osada
Hirotaka
H
Konishi
Hiroyuki
H
Tatematsu
Yoshio
Y
Yatabe
Yasushi
Y
Mitsudomi
Tetsuya
T
Fujii
Yoshitaka
Y
Takahashi
Takashi
T
D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011418:Prophase; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D012334:RNA, Neoplasm; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases