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Updated: Jun 20, 2026
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Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
19.4K
Nanopore-based consensus sequencing enables accurate multimodal tumor cell-free DNA profiling
Li-Ting Chen1,2, Myrthe Jager1,2, Dàmi Rebergen3
1Center for Molecular Medicine University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands.
Genome Research
|January 13, 2025
Summary
This study introduces NanoRCS, a novel method for noninvasive cancer monitoring using cell-free DNA. NanoRCS accurately estimates tumor fraction (TF) using single-nucleotide variations, copy number alterations, and fragmentomics, even at low levels.
Area of Science:
- Genomics and Bioinformatics
- Cancer Research and Diagnostics
Background:
- Shallow genome-wide cell-free DNA (cfDNA) sequencing is promising for noninvasive cancer monitoring.
- Detecting single-nucleotide variations (SNVs) is challenging at low sequencing depths due to errors.
- Multimodal cfDNA analysis (SNVs, CNAs, fragmentomics) can improve tumor fraction (TF) estimation.
Purpose of the Study:
- To develop a method for simultaneous multimodal TF estimation using cfDNA.
- To enable reliable detection of low tumor fractions for cancer monitoring.
- To provide a cost-effective and rapid solution for clinical cancer surveillance.
Main Methods:
- Developed Nanopore Rolling Circle Amplification (RCA)-enhanced Consensus Sequencing (NanoRCS).
- Utilized RCA and consensus calling with genome-wide long-read nanopore sequencing.
- Applied NanoRCS to analyze cfDNA from 18 cancer patients and 7 healthy controls.
Main Results:
- NanoRCS reliably detected tumor fractions as low as 0.24% in patient samples.
- In vitro experiments confirmed SNV measurements are crucial for detecting TFs below 3%.
- Simultaneous analysis of SNVs, CNAs, and fragmentomics enabled accurate multimodal TF estimation.
Conclusions:
- NanoRCS offers a robust approach for noninvasive cancer monitoring.
- The method facilitates accurate TF estimation, essential for personalized treatment strategies.
- NanoRCS presents a cost-effective and rapid solution for clinical applications in cancer care.
