The Longer, the Better? The Past, Present and the Future of Long Cell‐Free DNA‐Based Liquid Biopsy
L Y Lois Choy, Yuk Ming Dennis Lo
Abstract
ABSTRACT The use of cell‐free DNA (cfDNA) for liquid biopsy has become increasingly popular. However, the majority of research has primarily concentrated on short cfDNA molecules. After the recent studies identified long cfDNA in the plasma of cancer patients, healthy individuals, and pregnant women, further efforts have been made to explore low‐cost alternatives to long‐read sequencing and to understand the biology behind long cfDNA production. In this minireview, we present a summary of our recent knowledge about this emerging area of long cfDNA research and examine some of the challenges that may preclude its prompt use in the clinical setting. The distinctive genomic origin, epigenetic, and fragmentomic characteristics of long cfDNA provide exciting opportunities in developing novel approaches for cancer and prenatal testing. It is anticipated that with technological advancement and continuous research efforts, long cfDNA analysis will enhance our understanding of the biology of cfDNA generation, thereby providing an opportunity to improve our current liquid biopsy strategies.