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Updated: Oct 14, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Genomic Profiling of Blood-Derived Circulating Tumor DNA from Patients with Advanced Biliary Tract Cancer
Chen Chen1, Tao Wang1, Mengmei Yang2
1Hepatobiliary Surgery, Hunan Provincial People's Hospital (The First Affiliate Hospital of Hunan Normal University), Changsha, China.
Abstract:
Background: Biliary tract cancer is a highly lethal malignancy with poor clinical outcome. Accumulating evidence indicates targeted therapeutics may provide new hope for improving treatment response in BTC, hence better understanding the genomic profile is particularly important. Since tumor tissue may not be available for some patients, a complementary method is urgently needed. Circulating tumor DNA (ctDNA) provides a noninvasive means for detecting genomic alterations, and has been regarded as a promising tool to guide clinical therapies. Methods: Next-generation sequencing of 150 cancer-related genes was used to detect gene alterations in blood-derived ctDNA from 154 Chinese patients with BTC. Genomic alterations were analyzed and compared with an internal tissue genomic database and TCGA database. Results: 94.8% patients had at least one change detected in their ctDNA. The median maximum somatic allele frequency was 6.47% (ranging 0.1-34.8%). TP53 and KRAS were the most often mutated genes. The frequencies of single nucleotide variation in commonly mutated genes in ctDNA were similar to those detected in tissue samples, TP53 (35.1 vs. 40.4%) and KRAS (20.1 vs. 22.6%). Pathway analysis revealed that mutated genes were mapped to several key pathways including PI3K-Akt, p53, ErbB and Ras signaling pathway. In addition, patients harboring LRP1B, TP53, and ErbB family mutations presented significantly higher tumor mutation burden. Conclusions: These findings demonstrated that ctDNA testing by NGS was feasible in revealing genomic changes and could be a viable alternative to tissue biopsy in patients with metastatic BTC.
Insights
Circulating tumor DNA (ctDNA) testing using next-generation sequencing (NGS) is a feasible non-invasive method for detecting genomic alterations in biliary tract cancer (BTC). This approach can serve as a viable alternative to tissue biopsy for patients with metastatic BTC.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Biliary tract cancer (BTC) is a lethal malignancy with poor outcomes.
- Targeted therapies offer potential for improved treatment response, necessitating a deeper understanding of BTC's genomic profile.
- Limited availability of tumor tissue for analysis highlights the need for alternative diagnostic methods.
Purpose of the Study:
- To evaluate the feasibility and utility of next-generation sequencing (NGS) based circulating tumor DNA (ctDNA) analysis in Chinese patients with BTC.
- To identify common genomic alterations and affected pathways in BTC using ctDNA.
- To compare ctDNA findings with existing tissue genomic data.
Main Methods:
- Next-generation sequencing (NGS) was performed on blood-derived ctDNA from 154 Chinese patients with BTC, targeting 150 cancer-related genes.
- Genomic alterations detected in ctDNA were analyzed and compared with internal tissue genomic databases and The Cancer Genome Atlas (TCGA) database.
- Pathway analysis was conducted on mutated genes to identify significantly altered signaling pathways.
Main Results:
- Genomic alterations were detected in ctDNA of 94.8% of BTC patients.
- The most frequently mutated genes were TP53 and KRAS, with mutation frequencies in ctDNA closely mirroring those in tissue samples.
- Mutated genes were associated with key cancer-related pathways, including PI3K-Akt, p53, ErbB, and Ras signaling.
- Mutations in LRP1B, TP53, and ErbB family were linked to significantly higher tumor mutation burden.
Conclusions:
- ctDNA testing via NGS is a practical and effective method for identifying genomic alterations in patients with BTC.
- ctDNA analysis represents a promising non-invasive alternative to traditional tissue biopsy for guiding targeted therapies in metastatic BTC.
- These findings support the integration of ctDNA testing into the clinical management of BTC.
