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Circulating Tumor DNA Mutation Profiling by Targeted Next Generation Sequencing Provides Guidance for Personalized
Yongqian Shu1, Xue Wu2, Xiaoling Tong2
1Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Abstract:
Cancer is a disease of complex genetic alterations, and comprehensive genetic diagnosis is beneficial to match each patient to appropriate therapy. However, acquisition of representative tumor samples is invasive and sometimes impossible. Circulating tumor DNA (ctDNA) is a promising tool to use as a non-invasive biomarker for cancer mutation profiling. Here we implemented targeted next generation sequencing (NGS) with a customized gene panel of 382 cancer-relevant genes on 605 ctDNA samples in multiple cancer types. Overall, tumor-specific mutations were identified in 87% of ctDNA samples, with mutation spectra highly concordant with their matched tumor tissues. 71% of patients had at least one clinically-actionable mutation, 76% of which have suggested drugs approved or in clinical trials. In particular, our study reveals a unique mutation spectrum in Chinese lung cancer patients which could be used to guide treatment decisions and monitor drug-resistant mutations. Taken together, our study demonstrated the feasibility of clinically-useful targeted NGS-based ctDNA mutation profiling to guide treatment decisions in cancer.
Insights
Non-invasive liquid biopsies using circulating tumor DNA (ctDNA) enable comprehensive cancer mutation profiling. Targeted next-generation sequencing (NGS) identified actionable mutations in most patients, guiding personalized cancer therapy.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Cancer arises from complex genetic alterations, necessitating precise diagnosis for effective therapy.
- Obtaining tumor tissue samples for genetic analysis can be invasive and challenging.
- Circulating tumor DNA (ctDNA) offers a non-invasive biomarker for cancer mutation profiling.
Purpose of the Study:
- To evaluate the clinical utility of targeted next-generation sequencing (NGS) for ctDNA mutation profiling across diverse cancer types.
- To assess the concordance of ctDNA mutations with matched tumor tissues.
- To identify actionable mutations for guiding cancer treatment decisions.
Main Methods:
- Targeted NGS was performed on 605 ctDNA samples using a custom panel of 382 cancer-relevant genes.
- Mutation spectra from ctDNA were compared with matched tumor tissue data.
- Identification of clinically actionable mutations and associated therapeutic options.
Main Results:
- Tumor-specific mutations were detected in 87% of ctDNA samples.
- ctDNA mutation profiles showed high concordance with matched tumor tissues.
- 71% of patients harbored clinically actionable mutations, with 76% having drugs approved or in clinical trials.
- A unique mutation spectrum in Chinese lung cancer patients was identified.
Conclusions:
- Targeted NGS-based ctDNA mutation profiling is a feasible and clinically valuable approach for guiding cancer treatment.
- Non-invasive ctDNA analysis can identify actionable mutations, facilitating personalized therapy selection.
- This method holds potential for monitoring treatment response and detecting drug-resistant mutations.