Affiliation:
1. Weizmann Institute of Science
2. Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, the Hebrew University-Hadassah Medical School
Abstract
Cell-free DNA (cfDNA) tests use small amounts of DNA in the bloodstream as biomarkers. While it is thought that cfDNA is largely released by dying cells, the proportion of dying cells' DNA that reaches the bloodstream is unknown. Here, we integrate estimates of cellular turnover rates to calculate the expected amount of cfDNA. By comparing this to the actual amount of cell type-specific cfDNA, we estimate the proportion of DNA reaching plasma as cfDNA. We demonstrate that <10% of the DNA from dying cells is detectable in plasma, and the ratios of measured to expected cfDNA levels vary a thousand-fold among cell types, often reaching well below 0.1%. The analysis suggests that local clearance, presumably via phagocytosis, takes up most of the dying cells' DNA. Insights into the underlying mechanism may help to understand the physiological significance of cfDNA and improve the sensitivity of liquid biopsies.
Funder
Schwartz-Reisman collaborative science program
Yotam project
Mary and Tom Beck Canadian Center for Alternative Energy Research
Ulman Foundation
Leona M. and Harry B. Helmsley Charitable Trust
JDRF
National Institute of Diabetes and Digestive and Kidney Diseases
Grail
Publisher
eLife Sciences Publications, Ltd