Circulating tumor DNA functions as an alternative for tissue to overcome tumor heterogeneity in advanced gastric cancer
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Updated: Jul 27, 2026
Detection of Rare Mutations in CtDNA Using Next Generation Sequencing
Published on: August 24, 2017
Jing Gao1, Haixing Wang1, Wanchun Zang2
1Department of Gastrointestinal Oncology, Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, China.
Abstract:
Overcoming tumor heterogeneity is a major challenge for personalized treatment of gastric cancer, especially for human epidermal growth factor receptor-2 targeted therapy. Analysis of circulating tumor DNA allows a more comprehensive analysis of tumor heterogeneity than traditional biopsies in lung cancer and breast cancer, but little is known in gastric cancer. We assessed mutation profiles of ctDNA and primary tumors from 30 patients with advanced gastric cancer, then performed a comprehensive analysis of tumor mutations by multiple biopsies from five patients, and finally analyzed the concordance of HER2 amplification in ctDNA and paired tumor tissues in 70 patients. By comparing with a single tumor sample, ctDNA displayed a low concordance of mutation profile, only approximately 50% (138/275) somatic mutations were found in paired tissue samples, however, when compared with multiple biopsies, most DNA mutations in ctDNA were also shown in paired tumor tissues. ctDNA had a high concordance (91.4%, Kappa index = 0.784, P < 0.001) of HER2 amplification with tumor tissues, suggesting it might be an alternative for tissue. It implied that ctDNA-based assessment could partially overcome the tumor heterogeneity, and might serve as a potential surrogate for HER2 analysis in gastric cancer.
Insights
Circulating tumor DNA (ctDNA) analysis in advanced gastric cancer shows high concordance for HER2 amplification compared to tumor tissue. This suggests ctDNA may overcome tumor heterogeneity and serve as a surrogate for HER2 testing.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumor heterogeneity poses a significant challenge for personalized gastric cancer treatment, particularly for HER2-targeted therapies.
- Circulating tumor DNA (ctDNA) analysis offers a comprehensive approach to tumor heterogeneity assessment, yet its utility in gastric cancer remains underexplored.
Purpose of the Study:
- To evaluate the mutation profiles of ctDNA and primary tumors in advanced gastric cancer.
- To assess the concordance of HER2 amplification between ctDNA and tumor tissues.
- To determine if ctDNA can overcome tumor heterogeneity and serve as a surrogate for HER2 analysis.
Main Methods:
- Assessed mutation profiles of ctDNA and primary tumors in 30 advanced gastric cancer patients.
- Conducted comprehensive tumor mutation analysis using multiple biopsies from five patients.
- Analyzed HER2 amplification concordance between ctDNA and paired tumor tissues in 70 patients.
Main Results:
- ctDNA showed low concordance (approx. 50%) with single tumor samples but high concordance with multiple biopsies.
- A high concordance rate (91.4%) was observed for HER2 amplification between ctDNA and tumor tissues (Kappa = 0.784, P < 0.001).
Conclusions:
- ctDNA-based assessment can partially address tumor heterogeneity in gastric cancer.
- ctDNA analysis demonstrates potential as a surrogate for HER2 testing in gastric cancer, offering an alternative to tissue biopsy.
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