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Biol Pharm Bull. 2019;42(3):337-342. doi: 10.1248/bpb.b18-00804.

Recent Advances in Liquid Biopsy in Precision Oncology Research.

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DNA Chip Research Inc.
Laboratory of Medical Genomics in Nara Institute of Science and Technology.


Liquid biopsy is a minimally invasive test for cancer genetic status based on circulating tumor DNA (ctDNA), circulating tumor cells, or other tumor-derived materials in blood plasma. Although the minimal invasiveness and time resolution are attractive features of liquid biopsy, the limited amount of ctDNA in plasma poses problems. Recent developments in digital PCR and next-generation sequencing (NGS)-based technology have improved the accuracy of liquid biopsy. In particular, molecular barcoding technology in NGS-based methods, i.e., tagging of molecular barcodes to cell-free DNA before amplification, reduces technical errors by validating the consensus of sequences originating from a single molecule, leading to marked improvement of the accuracy and detection limit. However, substitutions caused by DNA damage and somatic mutations originating from normal cells are still obstacles to the sensitive detection of mutations on ctDNA. Since there have been only a few clinical applications, a deeper understanding of ctDNA biology and more advanced analytical technology are needed for the practical application of liquid biopsy.


circulating tumor DNA; liquid biopsy; minimally invasive tumor genotyping; molecular barcoding technology; ultrarare mutation detection

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