It is amazing how innovative diagnostic tests can now become established so quickly. At last year’s AACC Annual Scientific Meeting, Yuk-Ming Dennis Lo, PhD, described in the Wallace H. Coulter Lecture the advances and applications of circulating cell-free DNA (cfDNA) diagnostics. In an afternoon symposium today, “Precision Medicine Delivered by Advances in Circulating Cell-Free DNA Diagnostics,” attendees of this year’s meeting will learn how this versatile technology is routinely used in clinical practice.

At the symposium, Michael Oellerich, MD will speak about the application of cfDNA in organ transplant monitoring in female recipients and male donors. For transplantation medicine, the Holy Grail is just the right amount of immune-suppressant therapy: personalized, with no rejection, infection, or toxicity. Oellerich will explain how the presence of organ donor’s graft-derived cfDNA in receiver’s serum is a red flag of rejection. Detecting rejection of the transplanted organ early is important for some 316,000 living graft recipients in the U.S. With a huge shortage of donor organs, it is important to minimize rejection among graft recipients.

Oellerch also will show that cfDNA testing not only detects rejection earlier than traditional methods, but that it makes it easy and economical to personalize treatment in kidney, heart, lung, and liver transplants. CfDNA from the donor organ, with a plasma half-life of 15-30 minutes, is released in the recipient’s circulation by cellular necrosis (release of >10,000 base pair), apoptosis (180-200 mononucleosomal DNA), or active release. Therapeutic drug monitoring complements this testing by detecting drug toxicity. An added bonus of cfDNA testing is finding early infection. Oellerch will also discuss how the limitations of testing for male to female transplants will be overcome in the future when both donor and recipient whole genome analysis is more cost-effective.

Another speaker, Rossa Chiu, PhD, will reveal how cfDNA analysis can serve as a “total body scan” to find cancer early. Chiu will show how the source organs of cfDNA can be detected through droplet digital PCR, nanopore sequencing, and methylome analysis in clinical cases of pregnancy, hepatocellular carcinoma, and lymphoma. Amazingly, such advances almost sound like a Star Trek episode, except that here, instead of the legendary Tricorder, a blood test does all of the detection.

But that’s not all. In addition to these presentations, Glenn Palomaki, PhD, will elucidate another important application of the technology—the routine use of cfDNA-based prenatal screening. Palomaki will share his experience in the general pregnancy population offered by primary obstetrical care providers in Rhode Island. He will note that the main barriers to routine use of cfDNA testing are cost (which should fall as the test is increasingly used), and a failure rate of approximately 5.6%. Palomaki will also explain his prediction that cfDNA testing will continue to be used in conjunction with serum marker and ultrasound screenings.
This symposium will highlight the many important milestones that cfDNA analysis has reached. We all will certainly be looking forward to more advances in this field in the future.