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Updated: Jun 12, 2025
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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
The ATOM-Seq sequence capture panel can accurately predict microsatellite instability status in formalin-fixed tumour
Kanishta Srihar1, Arief Gusnanto2, Susan D Richman1,3
1Pathology and Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.
Scientific Reports
|September 19, 2024
Summary
Routine testing for microsatellite instability (MSI) in colorectal cancer (CRC) can now be efficiently performed alongside gene mutation analysis. A new method accurately detects MSI in FFPE samples, improving testing efficiency.
Area of Science:
- Oncology
- Genetics
- Molecular Diagnostics
Background:
- Microsatellite instability (MSI) is a key biomarker in various cancers, including colorectal cancer (CRC), and is associated with distinct clinical features compared to microsatellite stable (MSS) tumors.
- Routine MSI testing is increasingly recommended for specific cancer types to guide treatment decisions.
- Current diagnostic workflows often involve separate tests for gene mutations and MSI status.
Purpose of the Study:
- To evaluate the efficacy of a multiplex gene panel for simultaneous detection of MSI and gene mutations in formalin-fixed, paraffin-embedded (FFPE) colorectal cancer samples.
- To determine if a reduced number of MSI markers can maintain diagnostic accuracy.
- To assess the potential of integrating MSI testing into existing gene panel sequencing assays for improved efficiency.
Main Methods:
- Sequencing of tumor DNA from 335 FFPE CRC samples using a 23-gene panel (ATOM-Seq) incorporating 29 microsatellite regions.
- Comparison of sequencing-based MSI predictions with MMR status obtained from routine pathology reports.
- In silico analysis to determine the minimum number of MSI regions required for accurate classification.
Main Results:
- The integrated gene panel correctly classified MSI status in 314 out of 319 evaluable samples, achieving 98.4% concordance with routine pathology reports.
- Sixteen testing failures were noted.
- In silico analysis demonstrated that comparable performance could be achieved using as few as eight MSI marker positions.
- The method proved to be a quick and accurate means of determining MSI status in FFPE CRC samples.
Conclusions:
- Simultaneous detection of MSI and gene mutations using a single gene panel assay is feasible and highly accurate for FFPE CRC samples.
- This integrated approach can replace separate mutation and MSI testing without compromising accuracy, thereby enhancing overall testing efficiency in research and diagnostic settings.
