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.