Circulating free DNA in the era of precision oncology: Pre- and post-analytical concerns

Cancer treatment has entered the era of precision medicine, where knowledge of a patient's genetic profile is used to facilitate early diagnosis, drug selection, prognosis, prediction of drug responsiveness, the onset of secondary resistance, and relapse. Circulating free DNA (cfDNA) has emerged as an ideal source of genetic information for cancer patients, and numerous studies have explored its validity in various clinical applications. However, clinical implementation of cfDNA-based tests has been slow. In this review, we addressed some of the pre- and post-analytical issues regarding cfDNA tests. First, we summarized the characteristics of cfDNA and reviewed the methods used to identify tumor-derived cfDNA from the pool of total cfDNA. Second, we described the procedures used to extract cfDNA, which have a great impact on representativeness and yield. Finally, we discussed our thoughts on the validation of cfDNA-based tests and the reporting of test results amid drastic limitations.