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Updated: Jan 22, 2026
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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
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Negative Selection Maintains Grossly Altered but Broadly Stable Karyotypes in Metastatic Colorectal Cancer
William C H Cross1, Salpie Nowinski2,3, George D Cresswell3,4
1Rare Diseases and Cancer Evolution Lab, Centre for Cancer Research, School of Biological Sciences, University of Reading, Reading, United Kingdom.
Cancer Discovery
|January 21, 2026
Summary
Cancer progression involves a genetic bottleneck and copy number alterations (CNAs). Negative selection constrains cancer genome evolution after initiation, through metastasis and treatment.
Area of Science:
- Genomics
- Cancer Biology
- Evolutionary Dynamics
Background:
- Aneuploidy is common in cancer, impacting tumor biology.
- The evolutionary processes driving aneuploidy selection are not well understood.
Purpose of the Study:
- To investigate the temporal dynamics of copy number alterations (CNAs) during colorectal cancer progression.
- To understand the evolutionary constraints on cancer genomes from early stages to metastasis and treatment.
Main Methods:
- Longitudinal genomic analysis of 755 samples from 167 patients with colorectal neoplasias.
- Mathematical modeling to interpret copy number evolution patterns.
Main Results:
- Colorectal cancer progression involves a genetic bottleneck with increased CNAs and decreased clonal diversity.
- Cancer genomes appear constrained by negative selection on CNAs, maintaining similar karyotypes across stages, metastasis, and recurrence.
- Negative selection traps cancer genomes on specific fitness peaks.
Conclusions:
- Colorectal cancer progression requires navigating a rugged fitness landscape.
- Subsequent CNA evolution is significantly constrained by negative selection, influencing metastasis and treatment response.
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