title: Aberrant hypermethylation of the promoter region of the CHFR gene is rare in primary breast cancer.
abstract: Taxanes are among the most active agents and they are now known to be an indispensable component in chemotherapy for breast cancer. However, some patients are resistant to taxanes and the identification of the molecular characteristics that can predict the sensitivity to taxanes would be useful in selecting the most appropriate patients to receive taxane therapy. Taxanes are antimicrotubular agents that promote microtubular assembly and stabilize microtubules by preventing depolymerization. They interfere with normal mitotic transition and causes cell cycle arrest in the G2-M metaphase. CHFR (checkpoint with forkhead-associated and ring finger) is a recently identified gene, which functions as an important checkpoint protein early in G2-M transition. Its activation delays the cell cycle in prophase and promotes cell survival in response to the mitotic stress induced by either nocodazole or taxane. CHFR is frequently downregulated in human cancers, mostly owing to the hypermethylation of its promoter region. CHFR downregulation has been found in primary cancers or in the established tumor cells of various origins, such as the lung, colon, esophagus, and stomach. The aberrant hypermethylation of CHFR promoter appears to be a good molecular marker to predict sensitivity to taxanes in gastric, lung, and colon cancer. A downregulation of CHFR was observed in breast cancer cells, however, no apparent promoter hypermethylation has yet been reported. In addition, an alteration of the CHFR expression or aberrant promoter hypermethylation in primary breast cancer has not been fully investigated. In this study, we examined the methylation status of the promoter region of CHFR gene in 110 primary breast cancers. We observed the hypermethylation of the CHFR promoter region in only one case (0.9%). We herein show that the aberrant hypermethylation of this region is quite a rare event in primary breast carcinoma.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Higashi-ku, Japan. eriko@surg2.med.kyushu-u.ac.jp
authors.forename: Eriko
authors.initials: E
authors.lastname: Tokunaga
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.forename: Kojiro
authors.initials: K
authors.lastname: Nishida
authors.forename: Tadashi
authors.initials: T
authors.lastname: Koga
authors.forename: Rintaro
authors.initials: R
authors.lastname: Yoshida
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ikeda
authors.forename: Aya
authors.initials: A
authors.lastname: Kojima
authors.forename: Akinori
authors.initials: A
authors.lastname: Egashira
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: D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology; D018797:Cell Cycle Proteins / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases