Screening for ovarian cancer in women with endometriosis by using Fanconi DNA repair pathway

Tanja Pejovic, HongYan Liu, Farr Nezhat

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Objective: Cells from endometriotic foci sometimes exhibit genomic instability, which allows them to break chromosomes and behave as neoplastic cells. In order to achieve genomic instability, the cell has to tolerate DNA damage. Cells can achieve this by several mechanisms, including knocking out one of the 6 major DNA repair systems such as Fanconi anemia (FA) pathway. Fanconi anemia is a rare genetic disorder characterized by skeletal anomalies, progressive bone marrow failure, cancer susceptibility and cellular hypersensitivity to DNA cross-linking agents, such as mitomycin C and cisplatin. Materials and Methods: Seeking evidence of FA protein dysfunction in women with endometriosis, we screened ovarian surface epithelial cells from primary cultures established from 8 patients using cross-linker hypersensitivity assays. In chromosomal breakage assays, normal ovarian epithelial control cells were mitomycin C (MMC) resistant, but three of the eight samples (two with stage 4 endometriosis and one with stage 3 disease) were hypersensitive. Lymphocytes from all eight patients were MMC resistant. FANCD2 protein expression was reduced in these 3 cases. Ectopic expression of normal FANCD2 cDNA increased FANCD2 protein and induced MMC resistance in the three hypersensitive lines tested. Results: Therefore, in some women with endometriosis tissue-restricted hypersensitivity to cross-linking agents is a frequent finding, and chromosomal breakage responses to MMC may be a sensitive screening strategy to identify women with endometriosis who may be at risk at risk of ovarian cancer because cytogenetic instability identified in this way may antedate the onset of carcinoma. Discussion: Genetic or epigenetic events that result in tissue-specific FANCD2 gene suppression may represent a cause of this instability.

Original languageEnglish (US)
Pages (from-to)198-202
Number of pages5
JournalJournal of the Turkish German Gynecology Association
Volume8
Issue number2
StatePublished - Jun 1 2007

Keywords

  • Endometriosis
  • FANCD2
  • Fanconi anemia
  • Ovarian cancer

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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