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 language | English (US) |
|---|---|
| Pages (from-to) | 198-202 |
| Number of pages | 5 |
| Journal | Journal of the Turkish German Gynecology Association |
| Volume | 8 |
| Issue number | 2 |
| State | Published - Jun 1 2007 |
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Keywords
- Endometriosis
- FANCD2
- Fanconi anemia
- Ovarian cancer
ASJC Scopus subject areas
- Obstetrics and Gynecology
Cite this
Screening for ovarian cancer in women with endometriosis by using Fanconi DNA repair pathway. / Pejovic, Tanja; Liu, HongYan; Nezhat, Farr.
In: Journal of the Turkish German Gynecology Association, Vol. 8, No. 2, 01.06.2007, p. 198-202.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Screening for ovarian cancer in women with endometriosis by using Fanconi DNA repair pathway
AU - Pejovic, Tanja
AU - Liu, HongYan
AU - Nezhat, Farr
PY - 2007/6/1
Y1 - 2007/6/1
N2 - 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.
AB - 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.
KW - Endometriosis
KW - FANCD2
KW - Fanconi anemia
KW - Ovarian cancer
UR - http://www.scopus.com/inward/record.url?scp=34249898358&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249898358&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:34249898358
VL - 8
SP - 198
EP - 202
JO - Journal of the Turkish German Gynecology Association
JF - Journal of the Turkish German Gynecology Association
SN - 1309-0399
IS - 2
ER -