TY - JOUR
T1 - Limitations and opportunities of technologies for the analysis of cell-free DNA in cancer diagnostics
AU - Song, Ping
AU - Wu, Lucia Ruojia
AU - Yan, Yan Helen
AU - Zhang, Jinny X.
AU - Chu, Tianqing
AU - Kwong, Lawrence N.
AU - Patel, Abhijit A.
AU - Zhang, David Yu
N1 - Publisher Copyright:
© 2022, Springer Nature Limited.
PY - 2022/3
Y1 - 2022/3
N2 - Cell-free DNA (cfDNA) in the circulating blood plasma of patients with cancer contains tumour-derived DNA sequences that can serve as biomarkers for guiding therapy, for the monitoring of drug resistance, and for the early detection of cancers. However, the analysis of cfDNA for clinical diagnostic applications remains challenging because of the low concentrations of cfDNA, and because cfDNA is fragmented into short lengths and is susceptible to chemical damage. Barcodes of unique molecular identifiers have been implemented to overcome the intrinsic errors of next-generation sequencing, which is the prevailing method for highly multiplexed cfDNA analysis. However, a number of methodological and pre-analytical factors limit the clinical sensitivity of the cfDNA-based detection of cancers from liquid biopsies. In this Review, we describe the state-of-the-art technologies for cfDNA analysis, with emphasis on multiplexing strategies, and discuss outstanding biological and technical challenges that, if addressed, would substantially improve cancer diagnostics and patient care.
AB - Cell-free DNA (cfDNA) in the circulating blood plasma of patients with cancer contains tumour-derived DNA sequences that can serve as biomarkers for guiding therapy, for the monitoring of drug resistance, and for the early detection of cancers. However, the analysis of cfDNA for clinical diagnostic applications remains challenging because of the low concentrations of cfDNA, and because cfDNA is fragmented into short lengths and is susceptible to chemical damage. Barcodes of unique molecular identifiers have been implemented to overcome the intrinsic errors of next-generation sequencing, which is the prevailing method for highly multiplexed cfDNA analysis. However, a number of methodological and pre-analytical factors limit the clinical sensitivity of the cfDNA-based detection of cancers from liquid biopsies. In this Review, we describe the state-of-the-art technologies for cfDNA analysis, with emphasis on multiplexing strategies, and discuss outstanding biological and technical challenges that, if addressed, would substantially improve cancer diagnostics and patient care.
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U2 - 10.1038/s41551-021-00837-3
DO - 10.1038/s41551-021-00837-3
M3 - Review article
C2 - 35102279
AN - SCOPUS:85123930762
SN - 2157-846X
VL - 6
SP - 232
EP - 245
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 3
ER -