Detection of tumor-derived cell-free DNA from colorectal cancer peritoneal metastases in plasma and peritoneal fluid

Iris van't Erve, Koen P. Rovers, Alexander Constantinides, Karen Bolhuis, Emma C.E. Wassenaar, Robin J. Lurvink, Clément J. Huysentruyt, Petur Snaebjornsson, Djamila Boerma, Daan van den Broek, Tineke E. Buffart, Max J. Lahaye, Arend G.J. Aalbers, Niels F.M. Kok, Gerrit A. Meijer, Cornelis J.A. Punt, Onno Kranenburg, Ignace H.J.T. de Hingh, Remond J.A. Fijneman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Tumor-derived cell-free DNA (cfDNA) is an emerging biomarker for guiding the personalized treatment of patients with metastatic colorectal cancer (CRC). While patients with CRC liver metastases (CRC-LM) have relatively high levels of plasma cfDNA, little is known about patients with CRC peritoneal metastases (CRC-PM). This study evaluated the presence of tumor-derived cfDNA in plasma and peritoneal fluid (i.e. ascites or peritoneal washing) in 20 patients with isolated CRC-PM and in the plasma of 100 patients with isolated CRC-LM. Among tumor tissue KRAS/BRAF mutation carriers, tumor-derived cfDNA was detected by droplet digital polymerase chain reaction (ddPCR) in plasma of 93% of CRC-LM and 20% of CRC-PM patients and in peritoneal fluid in all CRC-PM patients. Mutant allele fraction (MAF) and mutant copies per ml (MTc/ml) were lower in CRC-PM plasma than in CRC-LM plasma (median MAF = 0.28 versus 18.9%, p < 0.0001; median MTc/ml = 21 versus 1,758, p < 0.0001). Within patients with CRC-PM, higher cfDNA levels were observed in peritoneal fluid than in plasma (median MAF = 16.4 versus 0.28%, p = 0.0019; median MTc/ml = 305 versus 21, p = 0.0034). These data imply that tumor-derived cfDNA in plasma is a poor biomarker to monitor CRC-PM. Instead, cfDNA detection in peritoneal fluid may offer an alternative to guide CRC-PM treatment decisions.

Original languageEnglish
Pages (from-to)203-208
Number of pages6
JournalJournal of Pathology: Clinical Research
Volume7
Issue number3
DOIs
Publication statusPublished - May 2021

Bibliographical note

Funding Information:
We thank Mirthe Lanfermeijer, Dorothé Linders, and Kalpana Ramkisoensing for laboratory assistance with the droplet digital PCR analyses. We thank Pien Delis‐van Diemen, Margriet Lemmens, Anne Bolijn, and Marianne Tijssen for laboratory assistance with the formalin‐fixed paraffin‐embedded (FFPE) DNA isolations. We acknowledge the NKI‐AVL Core Facility Molecular Pathology & Biobanking (CFMPB) for lab support. This work was funded by the ‘Stop Darmkanker Nederland’ Foundation and the Dutch Cancer Society (grant number 10438). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Funding Information:
We thank Mirthe Lanfermeijer, Doroth? Linders, and Kalpana Ramkisoensing for laboratory assistance with the droplet digital PCR analyses. We thank Pien Delis-van Diemen, Margriet Lemmens, Anne Bolijn, and Marianne Tijssen for laboratory assistance with the formalin-fixed paraffin-embedded (FFPE) DNA isolations. We acknowledge the NKI-AVL Core Facility Molecular Pathology & Biobanking (CFMPB) for lab support. This work was funded by the ?Stop Darmkanker Nederland? Foundation and the Dutch Cancer Society (grant number 10438). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Publisher Copyright:
© 2021 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland & John Wiley & Sons, Ltd.

Other keywords

  • ascitic fluid
  • biomarkers
  • circulating tumor DNA
  • colorectal neoplasms
  • liquid biopsy
  • peritoneum
  • plasma

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