Research Paper Volume 15, Issue 3 pp 777—790

Comparison of the mutation patterns between tumor tissue and cell-free DNA in stage IV gastric cancer

Ching-Yun Kung1,2, , Wen-Liang Fang1,2, , Yi-Ping Hung2,3, , Kuo-Hung Huang1,2, , Ming-Huang Chen2,3, , Yee Chao2,3, , Shih-Chieh Lin2,4, , Anna Fen-Yau Li2,5, , Su-Shun Lo2,6, , Chew-Wun Wu1,2, ,

  • 1 Department of Surgery, Division of General Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
  • 2 School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
  • 3 Department of Oncology, Center of Immuno-Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
  • 4 Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan
  • 5 Department of Anatomical Pathology, Cheng Hsin General Hospital, Taipei, Taiwan
  • 6 National Yang Ming Chiao Tung University Hospital, Yilan, Taiwan

Received: September 7, 2022       Accepted: February 1, 2023       Published: February 10, 2023
How to Cite

Copyright: © 2023 Kung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Compared to stage I–III gastric cancer (GC), the level of cell-free DNA (cfDNA) was significantly higher in stage IV GC. The mutation patterns of different metastatic patterns between cfDNA and tumor DNA in stage IV GC have not yet been reported. We used next-generation sequencing (NGS) to analyze cfDNA and tumor DNA in 56 stage IV GC patients. Tumor DNA and cfDNA were analyzed using a 29-gene NGS panel. In tumor samples, the most commonly mutated gene was TP53 (64%), followed by ARID1A (62%), KMT2C (60%) and KMT2D (58%). In cfDNA samples, the most commonly mutated genes were FAT4 (19%) and MACF1 (19%), followed by KMT2D (18%), ARID1A (14%) and LRP1B (14%). The concordance of mutation patterns in these 29 genes was 42.0% between cfDNA and tumor DNA. A specificity of 100% was found when using the mutation status of cfDNA to predict mutations in tumor samples. The sensitivity of the mutation status of cfDNA to predict mutation in tumor samples was highest in FAT4 (88.9%), followed by MACF1 (80%), CDH1 (75%) and PLB1 (75%). For cfDNA with PLB1 mutations, patients were more likely to develop distant lymphatic metastasis than peritoneal metastasis. Patients with multiple-site metastases had significantly more mutated spots than patients with single-site metastasis. Due to the high sensitivity and specificity of some genes in the prediction of mutation in tumor samples, monitoring the mutation pattern of cfDNA may be useful in the stage IV GC treatment.


AJCC: American Joint Committee on Cancer; CA 19-9: carbohydrate antigen 19-9; CEA: carcinoembryonic antigen; cfDNA: cell-free DNA; COSMIC: Catalogue of Somatic Mutations in Cancer; GC: Gastric cancer; NGS: Next-generation sequencing; PARP: poly ADP-ribose polymerase; PCR: Polymerase chain reaction; TCGA: The Cancer Genome Atlas; UICC: Union for International Cancer Control.