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Related Concept Videos

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Related Experiment Video

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Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
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Circulating Tumor DNA and Tissue Testing for Pancreatobiliary Tumors.

Himil Mahadevia1,2, Umair Majeed2, Jaydeepbhai Patel2

  • 1Department of Medicine, University of Missouri-Kansas City.

JAMA Network Open
|September 12, 2025
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Summary

Circulating tumor DNA (ctDNA) shows significant mutation concordance with tissue next-generation sequencing (NGS) for pancreatic cancer patients. This blood test may also help monitor treatment response and detect resistant clones.

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Area of Science:

  • Oncology
  • Molecular Diagnostics
  • Genomics

Background:

  • Pancreaticobiliary tumors have a poor prognosis, with tissue-based next-generation sequencing (NGS) identifying actionable alterations.
  • Limitations in tissue acquisition can hinder comprehensive genomic profiling.
  • Circulating tumor DNA (ctDNA) offers a less invasive alternative, but its concordance with tissue NGS requires investigation.

Purpose of the Study:

  • To determine the mutation concordance rate (mCR) between ctDNA and tissue NGS for pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CC).
  • To evaluate ctDNA's utility as a biomarker for treatment response in PDAC.

Main Methods:

  • Retrospective cohort study of 790 patients with PDAC and CC treated between 2014 and 2025.
  • Patients underwent ctDNA testing (1 platform) and tissue NGS (2 platforms).
  • Mutation concordance was calculated using Spearman correlation; treatment response was assessed via serial ctDNA, restaging scans, and CA19-9 levels.

Main Results:

  • Significant mCR was observed between ctDNA and tissue NGS in both PDAC (Spearman correlation=0.47) and CC (Spearman correlation=0.56).
  • Approximately 65% of patients showed shared gene alterations between ctDNA and tissue testing.
  • In PDAC, increased ctDNA variant allele frequency of TP53 and KRAS correlated with progressive disease.

Conclusions:

  • ctDNA testing demonstrates significant mutation concordance with tissue NGS in pancreaticobiliary tumors.
  • ctDNA shows potential for detecting resistant clones and monitoring treatment response in PDAC.
  • These findings support ctDNA as a valuable tool in managing advanced pancreaticobiliary cancers.