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Open Access 20-07-2023 | Current Opinion

‘Longing’ for the Next Generation of Liquid Biopsy: The Diagnostic Potential of Long Cell-Free DNA in Oncology and Prenatal Testing

Authors: Stephanie C. Y. Yu, L. Y. Lois Choy, Y. M. Dennis Lo

Published in: Molecular Diagnosis & Therapy | Issue 5/2023

Abstract

Liquid biopsy using cell-free DNA (cfDNA) has gained global interest as a molecular diagnostic tool. However, the analysis of cfDNA in cancer patients and pregnant women has been focused on short DNA molecules (e.g., ≤ 600 bp). With the detection of long cfDNA in the plasma of pregnant women and cancer patients in two recent studies, a new avenue of long cfDNA-based liquid biopsy has been opened. In this review, we summarize our current knowledge in this nascent field of long cfDNA analysis, focusing on the fragmentomic and epigenetic features of long cfDNA. In particular, long-read sequencing enabled single-molecule methylation analysis and subsequent determination of the tissue-of-origin of long cfDNA, which has promising clinical potential in prenatal and cancer testing. We also examine some of the limitations that may hinder the immediate clinical applications of long cfDNA analysis and the current efforts involved in addressing them. With concerted efforts in this area, it is hoped that long cfDNA analysis will add to the expanding armamentarium of liquid biopsy.

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Title: ‘Longing’ for the Next Generation of Liquid Biopsy: The Diagnostic Potential of Long Cell-Free DNA in Oncology and Prenatal Testing
Authors: Stephanie C. Y. Yu
L. Y. Lois Choy
Y. M. Dennis Lo
Publication date: 20-07-2023
Publisher: Springer International Publishing
Published in: Molecular Diagnosis & Therapy / Issue 5/2023
Print ISSN: 1177-1062
Electronic ISSN: 1179-2000
DOI: https://doi.org/10.1007/s40291-023-00661-2

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