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<p>Circulating tumor cell (CTC) clusters are highly efficient metastatic seeds in various cancers. Yet, their genetic heterogeneity and clonal architecture is poorly characterized. Using whole-exome sequencing coupled with phylogenetic inference from CTC clusters of patients with breast and prostate cancer, as well as mouse cancer models alongside barcode-mediated clonal tracking in vivo, we demonstrate oligoclonal composition of individual CTC clusters. These results improve our understanding of metastasis-relevant clonal dynamics.</p>

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Phylogenetic inference reveals clonal heterogeneity in circulating tumor cell clusters

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月2日

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  • David Gremmelspacher,
  • Johannes Gawron,
  • Barbara M. Szczerba,
  • Katharina Jahn,
  • Francesc Castro-Giner,
  • Jack Kuipers,
  • Jochen Singer,
  • Francesco Marass,
  • Ana Gvozdenovic,
  • Selina Budinjas,
  • Heike Pueschel,
  • Cyrill A. Rentsch,
  • Alfred Zippelius,
  • Viola Heinzelmann-Schwarz,
  • Christian Kurzeder,
  • Walter Paul Weber,
  • Christoph Rochlitz,
  • Marcus Vetter,
  • Niko Beerenwinkel,
  • Nicola Aceto

摘要

Circulating tumor cell (CTC) clusters are highly efficient metastatic seeds in various cancers. Yet, their genetic heterogeneity and clonal architecture is poorly characterized. Using whole-exome sequencing coupled with phylogenetic inference from CTC clusters of patients with breast and prostate cancer, as well as mouse cancer models alongside barcode-mediated clonal tracking in vivo, we demonstrate oligoclonal composition of individual CTC clusters. These results improve our understanding of metastasis-relevant clonal dynamics.