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Related Concept Videos

DNA Microarrays02:34

DNA Microarrays

Microarrays are high-throughput and relatively inexpensive assays that can be automated to analyze large quantities of data at a time. They are used in genome-wide studies to compare gene or protein expression under two varied conditions, such as healthy and diseased states. Microarrays consist of glass or silica slides on which probe molecules are covalently attached through surface functionalization. Most commonly, the slides are prepared through the chemisorption of silanes to silica...

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Related Experiment Video

Updated: Jun 20, 2026

Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
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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
PubMed
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.

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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.