Diagnostische bedeutung zirkulierender DNA- fragmente in der onkologie

The past decade witnessed an increasing interest in assessing circulating DNA in the plasma and serum of patients with malignant and non-malignant diseases. This might be due to the availability of new and sensitive methods for the determination of qualitative and quantitative changes in circulating DNA. As, previously, tumor-specific mutations or epigenetic modifications have been detected predominantly in tissue specimens, the appealing possibility to use less invasive though specific methods for tumor diagnosis was a noticeable incentive for the exploration of circulating DNA. A considerable part of the circulating DNA, which is mostly present in serum and plasma as nucleosomal DNA, is released during apoptotic cell death. Because the rate of apoptosis is deregulated in many pathological situations such as degenerative, traumatic, ischemic, inflammatory, and malignant diseases, and because many cytotoxic therapies aim at reducing the cancer cell number by apoptosis, the cell death product "circulating DNA" might serve as an attractive and appropriate biochemical correlative. In this review, the physiological and pathophysiological background of the arrangement of DNA as nucleosomes and of its release into circulation is shown. Further, the metabolism of circulating DNA in plasma and serum and its role in the pathogenesis of various diseases is discussed. Finally, the diagnostic relevance of qualitative and quantitative changes in circulating DNA for screening, differential diagnosis, prognosis, monitoring of systemic therapies, early prediction of therapy response and detection of recurrence in malignant diseases is reviewed. Concluding, some methodical considerations regarding the measurement of circulating DNA are given.