Korean J Clin Oncol.  2023 Dec;19(2):45-51. 10.14216/kjco.23009.

Concordance of circulating tumor DNA and matched formalin-fixed paraffin-embedded tumor tissue in gastric cancer as a predictor of recurrence

Affiliations
  • 1Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
  • 2Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
  • 3Department of Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul, Korea
  • 4Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
  • 5Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
  • 6Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

Abstract

Purpose
Combined analysis of the variant composition of circulating tumor DNA (ctDNA) from cell-free plasma and DNA from tumor tissue could provide insight into the implications of the genetic alterations responsible for the intratumoral and intertumoral heterogeneity of gastric cancer. We aimed to evaluate the usefulness of this approach in these patients.
Methods
Cell-free plasma and formalin-fixed paraffin-embedded tumor tissue samples from 46 patients with gastric cancer were examined. Targeted deep sequencing was performed using a commercially available kit.
Results
The cell-free DNA (cfDNA) concentration was higher in stage II-IV versus stage I patients and in larger versus smaller tumors. Only 12 of the 36 (33.3%) alterations in the tumor tissue samples were in concordance with those in the ctDNA samples. Two variants were in concordance in stage I samples and 10 in stage II-IV samples. Actionable variants that were detected in concordance were in the stage II-IV samples. Preoperative ctDNA positivity of actionable variants was significantly associated with cfDNA concentration, lymphatic invasion, N stage, and TNM stage. Cancer recurrence was significantly associated with tumor size, lymphatic/vascular invasion, TNM stage, and ctDNA-tumor tissue variant concordance.
Conclusion
Preoperative ctDNA genetic analysis using a multigene panel offers substantial clinical benefits when performed in conjunction with targeted deep sequencing of tumor tissue. Concordance between preoperative ctDNA and tumor tissue mutations may serve as a prognostic indicator in patients with gastric cancer.

Keyword

Stomach neoplasms; Circulating tumor DNA; Tissues; High-throughput nucleotide sequencing; Recurrence
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