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Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
Published on: October 18, 2013
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Genome-scale mutational signature analysis in archived fixed tissues
Bérénice Chavanel1, François Virard2, Vincent Cahais1
1International Agency for Research on Cancer, Epigenomics and Mechanisms Branch, Lyon, France.
Mutation Research. Reviews in Mutation Research
|August 31, 2024
Summary
Next-generation sequencing reveals mutational signatures in archived tissues, distinguishing true cancer causes from fixation artifacts. This advances understanding of cancer development and prevention strategies.
Area of Science:
- Genomics
- Cancer Research
- Molecular Biology
Background:
- Mutation spectra and signatures are key to understanding cancer development.
- Massively parallel sequencing (next-generation sequencing) is established for analyzing these signatures.
- Analysis of archived, fixed biospecimens remains an underexplored area for genome-scale mutational signature studies.
Purpose of the Study:
- To review the application of next-generation sequencing (NGS) in analyzing mutational signatures in archived fixed tissues.
- To explore the potential of these signatures as markers for mutagenic exposures and their impact on cancer driver events.
- To differentiate true biological mutagenic signatures from artifactual signatures caused by tissue fixation.
Main Methods:
- Utilizing established next-generation sequencing techniques, including whole-exome and whole-genome sequencing.
- Applying error-corrected/duplex sequencing for enhanced accuracy.
- Analyzing formalin-fixed or alcohol-fixed paraffin-embedded (FFPE) archived biospecimens.
Main Results:
- Demonstrated successful application of NGS methodologies in archived fixed tissues.
- Successfully delineated tissue fixation-related DNA damage, creating artifactual signatures.
- Distinguished artifactual signatures from true biological mutagenic signatures.
Conclusions:
- NGS applied to archived fixed biospecimens enhances understanding of cancer causes.
- Identifies mutagenic effects of extrinsic cancer risk agents.
- Provides implications for prevention efforts by highlighting avoidable cancer-causing exposures.
Keywords:
DNA damage artifactsFormalin-fixed paraffin-embedded tissueMutation spectrumMutational signature analysisNext-generation sequencingMore Related Videos
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