title: Relationship of aberrant DNA hypermethylation of CHFR with sensitivity to taxanes in endometrial cancer.
abstract: The relationship of aberrant DNA hypermethylation of cell cycle checkpoint genes with the sensitivity of cancer cells to anticancer drugs is a question of current interest. In this study, we investigated the relationship between aberrant hypermethylation of the CHFR (checkpoint with forkhead-associated and ring finger) mitotic checkpoint gene and sensitivity to taxanes in endometrial cancer. Methylation-specific PCR (MSP) indicated aberrant hypermethylation of CHFR in 12.0% (6/50) of endometrial cancer specimens, and suggested that aberrant hypermethylation is significantly more frequent in poorly differentiated adenocarcinoma (G3) (p<0.05). Of six culture cell lines, SNG-II and HEC108 cells showed aberrant hypermethylation and reduced expression of CHFR. These cells had high sensitivity to taxanes but became resistant after demethylation. Cancer specimens with aberrant hypermethylation of CHFR also exhibited high sensitivity to taxanes. To our knowledge, this study is the first to examine aberrant hypermethylation of CHFR in endometrial cancer, and our results suggest that the methylation status of CHFR may be a new molecular index that will allow design of personalized treatment in endometrial cancer. This may be particularly important in poorly differentiated adenocarcinoma (G3), which is known to have a poor prognosis.
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Shinanomachi 55, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Yanokura
authors.forename: Kouji
authors.initials: K
authors.lastname: Banno
authors.forename: Makiko
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Nobumaru
authors.initials: N
authors.lastname: Hirao
authors.forename: Akira
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Susumu
authors.forename: Katsumi
authors.initials: K
authors.lastname: Tsukazaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019175:DNA Methylation; D000077209:Decitabine; D000077143:Docetaxel; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology*; D044767:Ubiquitin-Protein Ligases
chemical_list: D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D043823:Taxoids; D000077143:Docetaxel; D000077209:Decitabine; D004317:Doxorubicin; C412002:CHFR protein, human; D044767:Ubiquitin-Protein Ligases; D001374:Azacitidine; D017239:Paclitaxel; D002945:Cisplatin