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.

Clinical trial, Fanconi genes, Ovarian cancer, Platinum resistance,
British Journal of Cancer
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Erasmus MC: University Medical Center Rotterdam

Lim, S.L, Smith, P, Syed, N, Coens, C, Wong, H, van der Burg, M, … Green, J.A. (2008). Promoter hypermethylation of FANCF and outcome in advanced ovarian cancer. British Journal of Cancer, 98(8), 1452–1456. doi:10.1038/sj.bjc.6604325