Cell-free DNA testing: future applications in gastroenterology and hepatology

Abstract

The application of next-generation sequencing in clinical practice is increasing as accuracy and interpretation have improved and the cost continues to decline rapidly. Cell-free DNA is a unique source for next-generation sequencing that could change routine clinical practice in gastroenterology and hepatology. Testing of cell-free DNA in blood and fecal samples is an easy, rapid, and noninvasive method to assess for premalignant, malignant, metabolic, infectious, inflammatory, and autoimmune gastrointestinal and liver diseases. In this review, we describe cell-free DNA technologies, current applications of cell-free DNA testing, and proposed cell-free DNA targets for gastrointestinal and hepatic diseases, with a specific focus on malignancy. In addition, we provide commentary on how cell-free DNA can be integrated into clinical practice and help guide diagnosis, prognosis, disease management, and therapeutic response.

Keywords: cell-free DNA; gastroenterology and hepatology; individualized medicine.

Figure 1.

Sources of cell-free DNA (cfDNA). cfDNA is released by all tissues of the body including during normal function, but also by sources with differential or abnormal function such as gut flora or cancer (blue lines). cfDNA is usually understood to be in the plasma, but can also be found in other bodily fluids such as the bile, feces, and urine.

Figure 2.

Methods of detecting cell-free DNA. ARMS, amplification-refractory mutation system; NGS, next generation sequencing; PCR, polymerase chain reaction; QPCR, quantitative real-time PCR.