Transplantation Monitoring by Plasma DNA Sequencing

Over the past 15 years, there has been increasing interest in the use of cell-free nucleic acids in plasma for molecular diagnostics, especially for cancer detection and prenatal diagnosis. In 1998, Lo et al. showed that donor-derived DNA sequences could be detected in the plasma of transplant recipients (1). This group further showed that different transplanted organs—e.g., the heart, liver, and kidney—appeared to release different amounts of DNA into the plasma, probably relating to the size of the organ (2). Furthermore, details in the design of the molecular assay have been shown to have important implications for detecting circulating donor-derived DNA. For example, the use of a detection target, DYS14 (1,3), which is a member of a multicopy Y chromosome–specific gene, TSPY1 3 (testis specific protein, Y-linked 1), has produced a higher sensitivity in detecting circulating donor-derived DNA than when the single-copy gene SRY (sex-determining region Y) is used (2).As cell death is generally accepted to be an important reason for the release of DNA into the plasma, Lo et al. further hypothesized that the measurement of donor-derived DNA in the plasma of transplant recipients might be used for monitoring graft rejection (1). This hypothesis has subsequently been shown to be correct by a number of independent workers (4),(5). The usefulness of this strategy depends, however, on the ability to design molecular assays that allow the detection of donor-specific DNA sequences. Most workers in this field have thus far used …