What fraction of cellular DNA turnover becomes cfDNA?

Ron Sender, Elad Noor, Ron Milo, Yuval Dor

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageAmerican English
JournaleLife
Volume12
DOIs
StatePublished - 26 Feb 2024

Bibliographical note

Publisher Copyright:
© 2023, Sender et al.

Keywords

  • cellular turnover
  • cfDNA
  • clearance mechanisms
  • computational biology
  • human
  • liquid biopsy
  • systems biology

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