Promoter hypermethylation of FANCF and outcome in advanced ovarian cancer

Br J Cancer. 2008 Apr 22;98(8):1452-6. doi: 10.1038/sj.bjc.6604325. Epub 2008 Apr 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cisplatin / therapeutic use
  • CpG Islands
  • DNA Methylation*
  • Fanconi Anemia Complementation Group F Protein / genetics*
  • Female
  • Humans
  • Neoplasms, Glandular and Epithelial / genetics
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Promoter Regions, Genetic*

Substances

  • FANCF protein, human
  • Fanconi Anemia Complementation Group F Protein
  • Cisplatin