Clinical use of circulating nucleosomes.

Nucleosomes, complexes of DNA and histone proteins, are released from dying and stressed cells into the blood circulation. Concentrations of circulating nucleosomes in plasma and serum are frequently found to be elevated in various cancers, and also in such acute conditions as stroke, trauma, and sepsis as well as in autoimmune diseases. The first part of this review focuses on the structural and functional properties of nucleosomes, the potential sources of nucleosome release into the circulation, the metabolism of circulating nucleosomes, and their pathophysiological role in disease. It goes on to describe the relevance of circulating nucleosomes in the diagnosis and prognosis of non-malignant conditions such as sepsis, stroke, and autoimmune disease. Finally, it describes the clinical value of nucleosomes in the diagnosis, staging, prognosis, and monitoring of therapy in cancer; in particular, their potential as a new diagnostic tool for the early estimation of response to cytotoxic cancer therapy is emphasized.