The Origin of Highly Elevated Cell-Free DNA in Healthy Individuals and Patients with Pancreatic, Colorectal, Lung, or Ovarian Cancer

Austin K. Mattox, Christopher Douville, Yuxuan Wang, Maria Popoli, Janine Ptak, Natalie Silliman, Lisa Dobbyn, Joy Schaefer, Steve Lu, Alexander H. Pearlman, Joshua D. Cohen, Jeanne Tie, Peter Gibbs, Kamel Lahouel, Chetan Bettegowda, Ralph H. Hruban, Cristian Tomasetti, Peiyong Jiang, K. C.Allen Chan, Yuk Ming Dennis LoNickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein

Research output: Contribution to journalArticlepeer-review

Abstract

Cell-free DNA (cfDNA) concentrations from patients with cancer are often elevated compared with those of healthy controls, but the sources of this extra cfDNA have never been determined. To address this issue, we assessed cfDNA methylation patterns in 178 patients with cancers of the colon, pancreas, lung, or ovary and 64 patients without cancer. Eighty-three of these individuals had cfDNA concentrations much greater than those generally observed in healthy subjects. The major contributor of cfDNA in all samples was leukocytes, accounting for ∼76% of cfDNA, with neutrophils predominating. This was true regardless of whether the samples were derived from patients with cancer or the total plasma cfDNA concentration. High levels of cfDNA observed in patients with cancer did not come from either neoplastic cells or surrounding normal epithelial cells from the tumor’s tissue of origin. These data suggest that cancers may have a systemic effect on cell turnover or DNA clearance. SIGNIFICANCE: The origin of excess cfDNA in patients with cancer is unknown. Using cfDNA methylation patterns, we determined that neither the tumor nor the surrounding normal tissue contributes this excess cfDNA—rather it comes from leukocytes. This finding suggests that cancers have a systemic impact on cell turnover or DNA clearance.

Original languageEnglish (US)
Pages (from-to)2166-2179
Number of pages14
JournalCancer discovery
Volume13
Issue number10
DOIs
StatePublished - 2023

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'The Origin of Highly Elevated Cell-Free DNA in Healthy Individuals and Patients with Pancreatic, Colorectal, Lung, or Ovarian Cancer'. Together they form a unique fingerprint.

Cite this