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Related Experiment Video

Updated: Sep 5, 2025

Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment
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Interrogating breast cancer heterogeneity using single and pooled circulating tumor cell analysis.

Françoise Rothé1, David Venet1, Dieter Peeters2,3

  • 1Breast Cancer Translational Research Laboratory J.-C. Heuson, Université Libre de Bruxelles, Institut Jules Bordet, Brussels, Belgium.

NPJ Breast Cancer
|July 5, 2022
PubMed
Summary

Circulating tumor cells (CTCs) complement tumor biopsies for genomic profiling in metastatic breast cancer. Analyzing CTCs and biopsies reveals tumor heterogeneity and evolution, aiding treatment resistance insights.

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Area of Science:

  • Oncology
  • Genomics
  • Cancer Biology

Background:

  • Single-cell technologies enable detailed analysis of tumor heterogeneity, crucial for understanding tumor evolution and treatment resistance.
  • Circulating tumor cells (CTCs) are increasingly explored as a non-invasive source for tumor genomic profiling.

Purpose of the Study:

  • To investigate whether CTCs can complement metastatic biopsies for comprehensive tumor genomic profiling.
  • To compare mutational and copy number aberration (CNA) profiles between CTCs and matched tumor biopsies.

Main Methods:

  • Characterization of 11 single CTCs and 10 pooled CTC samples at mutational and CNA levels.
  • Comparison of CTC genomic data with matched synchronous tumor biopsies from three metastatic breast cancer patients (TNBC, HER2+, ER+).

Main Results:

  • Similar CNA profiles and driver mutations were observed between bulk tissue and CTCs in HER2-positive and triple-negative breast cancer (TNBC) tumors.
  • Distinct CNA profiles and driver mutations, including two clones (ESR1 Y537N and TP53), were identified in the estrogen receptor-positive (ER+) tumor's CTCs compared to its biopsy.
  • De novo mutational signatures from CTCs elucidated patient-specific biological processes.

Conclusions:

  • CTCs and tumor tissue provide complementary clinical information for mapping tumor heterogeneity and evolution.
  • CTC analysis offers valuable insights into tumor clonal dynamics and patient-specific biological processes.