What fraction of cellular DNA turnover becomes cfDNA?

Elife

Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, the Hebrew University-Hadassah Medical School, Jerusalem, Israel.

Published: February 2024

AI Article Synopsis

  • * By analyzing the turnover rates of different cell types, the researchers found significant variations, with detectable cfDNA levels varying a thousand-fold across cell types, often dropping below 0.1%.
  • * The findings indicate that most cfDNA is likely removed from circulation through local clearance processes like phagocytosis, which could enhance our understanding of cfDNA's role in the body and improve liquid biopsy techniques.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10942627PMC
http://dx.doi.org/10.7554/eLife.89321DOI Listing

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