Levels of circulating cell-free nuclear and mitochondrial DNA in benign and malignant ovarian tumors

OBJECTIVE: To analyze the levels of circulating cell-free nuclear DNA and circulating cell-free mitochondrial DNA in patients with benign and malignant ovarian tumors using a gold-standard assay and to investigate whether quantitative alterations of the circulating cell-free species have values in the management of the patients. METHODS: One hundred four patients were recruited for this study. We developed a quantitative, multiplex polymerase chain reaction to measure the levels of circulating cell-free nuclear DNA and circulating cell-free mitochondrial DNA in serum and plasma of patients with epithelial ovarian cancer, benign epithelial ovarian tumors, or endometriosis. The levels of the circulating cell-free DNA were compared with those of a healthy, age-matched control group. RESULTS: The patients with epithelial ovarian cancer had significantly higher amounts of circulating cell-free nuclear DNA and circulating cell-free mitochondrial DNA in plasma compared with the healthy control group (mean of nuclear DNA 10,723/2,591 and mean of mitochondrial DNA 4,918,978/2,294,264, P=.009 and 0.022, respectively) and with the other group with benign ovarian diseases (mean of nuclear DNA 10,723/2,965 and mean of mitochondrial DNA 4,918,978/1,597,551, P=.027 and 0.002, respectively). However, no relationship between levels of the circulating cell-free DNA and the pathological parameters as well as CA 125 measurement in patients with epithelial ovarian cancer was found. A significant difference between the epithelial ovarian cancer and endometriosis group was found in circulating cell-free mitochondrial DNA but not in circulating cell-free nuclear DNA (mean of mitochondrial DNA 4,918,978/2,273,988 and mean of nuclear DNA 10,723/3,291, P=.013 and 0.105, respectively). CONCLUSION: Elevated levels of circulating cell-free nuclear DNA and circulating cell-free mitochondrial DNA in epithelial ovarian cancer may have diagnostic value. Our finding suggests that the circulating molecules might be potential biomarkers in the disease.     

The placenta as witness

The placenta not only "records" and reflects the intrauterine environment, it also provides valuable information on the cause and timing of many adverse events and conditions. The placenta may be useful in several ways. It may be the cause of injury due to an inherent abnormality, it may "malfunction" because of disease processes that are not primarily placental in origin, or it may merely reflect an abnormal intrauterine environment. Not only may the etiology of the injury be ascertained from placental examination, but also a time frame during which the abnormal condition has been operating. Acute lesions may be associated with sudden catastrophic events, whereas other, more chronic lesions lead to decreased placental reserves. Markedly depleted reserves will render the infant susceptible to other, sometimes more acute, events and thus are also associated with significant injury or even death.