4.7 Article

Graphical abstract

Journal

JCI INSIGHT
Volume 7, Issue 2, Pages -

Publisher

AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/jci.insight.153559

Keywords

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Funding

  1. Grail
  2. Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine
  3. Alex U. Soyka pancreatic cancer fund
  4. Israel Science Foundation
  5. Waldholtz/Pakula family
  6. Robert and Marilyn Sternberg Charitable Foundation
  7. Grant for Multiple Sclerosis Innovation from Merck
  8. Israel Cancer Research Fund
  9. Hale Family Center for Pancreatic Cancer Research
  10. Lustgarten Foundation Dedicated Pancreatic Cancer Research Laboratory program
  11. NIH [U01 CA210171]
  12. Ministry of Science and Technology, Israel

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By utilizing tissue-specific methylation patterns of circulating cell-free DNA (cfDNA), cell death in organs affected by cancer can be detected, potentially aiding in early cancer detection and identifying the presence of metastases.
Cancer inflicts damage to surrounding normal tissues, which can culminate in fatal organ failure. Here, we demonstrate that cell death in organs affected by cancer can be detected by tissue specific methylation patterns of circulating cell-free DNA (cfDNA). We detected elevated levels of hepatocyte-derived cfDNA in the plasma of patients with liver metastases originating from different primary tumors, compared with cancer patients without liver metastases. In addition, patients with localized pancreatic or colon cancer showed elevated hepatocyte cfDNA, suggesting liver damage inflicted by micrometastatic disease, by primary pancreatic tumor pressing the bile duct, or by a systemic response to the primary tumor. We also identified elevated neuron-, oligodendrocyte-, and astrocyte-derived cfDNA in a subpopulation of patients with brain metastases compared with cancer patients without brain metastasis. Cell type-specific cfDNA methylation markers enable the identification of collateral tissue damage in cancer, revealing the presence of metastases in specific locations and potentially assisting in early cancer detection.

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