The Long and Short of Circulating Cell-Free DNA and the Ins and Outs of Molecular Diagnostics

The discovery of cell-free tumor and fetal DNA molecules in the plasma of cancer patients and pregnant women, respectively, has opened up exciting opportunities in molecular diagnosis. The understanding of the biological properties of circulating cell-free DNA (cfDNA) molecules would be essential for us to make the best use of such molecules in different clinical settings. In this review we start by exploring the technologies that have been used for analyzing the size profiles of cfDNA in plasma. We then review the size profiles of cfDNA in different clinical scenarios, including cancer, pregnancy, transplantation, and autoimmune diseases. Finally, we discuss the potential diagnostic applications of plasma DNA size profiling.

TrendsFetus-derived DNA molecules in the plasma of pregnant women are shorter than maternal DNA molecules.DNA derived from tumor cells is shorter than that from non-malignant cells in the plasma of cancer patients.Size differences between different species of circulating DNA can be used for developing size-based molecular diagnostics, as exemplified by recent efforts in noninvasive prenatal testing and cancer testing.