title: Promoter hypermethylation of FANCF and outcome in advanced ovarian cancer.
abstract: The Fanconi gene family has a role in DNA repair and inactivation of FANCF has been proposed as a mechanism of sensitisation to platinum chemotherapy. This study sought to confirm this hypothesis in cell lines and a large series of ovarian cancer samples. Promoter methylation was assessed by methylation-sensitive polymerase chain reaction of FANCF in nine ovarian cancer cell lines and 74 ovarian cancer samples taken from patients entered on a trial of cisplatin-based chemotherapy. This study confirmed methylation-dependent silencing of FANCF in one out of nine ovarian cancer cell lines. Methylation of FANCF was demonstrated in 13.2% of 53 evaluable ovarian tumour samples. Progression-free survival gave an HR of 3.63 (95% CI: 1.54-8.54, P=0.0016) in favour of the unmethylated cases. There was no association with overall survival. This study does not support methylation-dependent silencing of FANCF as a mechanism of sensitisation to platinum-based chemotherapy in ovarian cancer.
authors.affiliation: Division of Surgery and Oncology, School of Cancer Studies, University of Liverpool, Liverpool, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Lim
authors.forename: P
authors.initials: P
authors.lastname: Smith
authors.forename: N
authors.initials: N
authors.lastname: Syed
authors.forename: C
authors.initials: C
authors.lastname: Coens
authors.forename: H
authors.initials: H
authors.lastname: Wong
authors.forename: M
authors.initials: M
authors.lastname: van der Burg
authors.forename: P
authors.initials: P
authors.lastname: Szlosarek
authors.forename: T
authors.initials: T
authors.lastname: Crook
authors.forename: J A
authors.initials: JA
authors.lastname: Green
mesh_terms: D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D018899:CpG Islands; D019175:DNA Methylation; D052219:Fanconi Anemia Complementation Group F Protein / Q000235:genetics*; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011401:Promoter Regions, Genetic
chemical_list: C499901:FANCF protein, human; D052219:Fanconi Anemia Complementation Group F Protein; D002945:Cisplatin