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Phylogenetic inference reveals clonal heterogeneity in circulating tumor cell clusters
David Gremmelspacher1, Johannes Gawron2,3, Barbara M Szczerba4
1Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.
Nature Genetics
|June 2, 2025
Summary
Circulating tumor cell (CTC) clusters are key to cancer metastasis. This study reveals CTC clusters are oligoclonal, meaning they comprise multiple distinct cell clones, improving understanding of cancer spread.
Area of Science:
- Oncology
- Genetics
- Cancer Biology
Background:
- Circulating tumor cell (CTC) clusters are recognized as potent drivers of cancer metastasis.
- The internal genetic diversity and clonal structure within CTC clusters remain largely uncharacterized.
Purpose of the Study:
- To investigate the genetic heterogeneity and clonal architecture of circulating tumor cell (CTC) clusters.
- To understand the clonal dynamics contributing to cancer metastasis.
Main Methods:
- Whole-exome sequencing of CTC clusters from breast and prostate cancer patients.
- Phylogenetic inference to analyze genetic relationships within CTCs.
- Barcode-mediated clonal tracking in vivo using mouse cancer models.
Main Results:
- Demonstrated that individual CTC clusters exhibit an oligoclonal composition.
- Identified distinct clonal populations within single CTC clusters.
- Provided insights into the in vivo behavior and evolution of CTC clones.
Conclusions:
- CTC clusters are not monoclonal but composed of multiple genetically distinct cell populations.
- Understanding the oligoclonal nature of CTC clusters is crucial for deciphering metastatic processes.
- This research enhances knowledge of clonal dynamics in cancer metastasis.
