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Updated: Jun 27, 2026
09:45
Detection of Copy Number Alterations Using Single Cell Sequencing
Published on: February 17, 2017
DNA copy-number alterations underlie gene expression differences between microsatellite stable and unstable
Robert N Jorissen1, Lara Lipton, Peter Gibbs
1Ludwig Colon Cancer Initiative Laboratory, Ludwig Institute for Cancer Research, Parkville, Victoria, Australia.
Summary
Microsatellite instability (MSI) in colorectal cancer shows consistent gene expression changes across studies. DNA copy-number changes partly explain these gene expression differences between MSI and microsatellite-stable (MSS) tumors.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Microsatellite instability (MSI) occurs in ~15% of colorectal cancers.
- MSI-associated gene expression signatures are inconsistent across studies.
- Causes and effects of differential gene expression in MSI colorectal cancer are poorly understood.
Purpose of the Study:
- Assess the consistency of MSI-associated gene expression changes in colorectal cancer across multiple studies.
- Validate a gene expression-based classifier for MSI status.
- Investigate the causes of differential gene expression in MSI vs. MSS colorectal cancer.
Main Methods:
- Analyzed DNA microarray data from 89 MSI and 140 microsatellite-stable (MSS) colorectal cancers, plus external datasets.
- Assessed cross-study consistency of MSI-associated gene expression changes.
- Validated MSI classifier performance using independent test sets.
- Performed functional category analysis and compared gene expression with DNA copy-number data.
Main Results:
- MSI-associated gene expression changes were highly consistent across studies (P < 0.001).
- A gene expression classifier accurately predicted MSI status (96% sensitivity, 85% specificity).
- Immune response genes were upregulated; cell adhesion and metabolism genes were downregulated in MSI tumors.
- Differential gene expression correlated with DNA copy-number aberrations (P < 0.001).
Conclusions:
- MSI-associated gene expression changes in colorectal cancer are consistent across studies.
- DNA copy-number alterations contribute to gene expression differences between MSI and MSS colorectal cancers.
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