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

Ching Yun Kung, Wen Liang Fang, Yi Ping Hung, Kuo Hung Huang*, Ming Huang Chen, Yee Chao, Shih Chieh Lin, Anna Fen Yau Li, Su Shun Lo, Chew Wun Wu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)777-790
Number of pages14
JournalAging
Volume15
Issue number3
DOIs
StatePublished - 2023

Keywords

  • NGS
  • cfDNA
  • sensitivity
  • specificity
  • tumor DNA

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