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Phylogenetic inference reveals clonal heterogeneity in circulating tumor cell clusters
Nature Genetics ( IF 31.7 ) Pub Date : 2025-06-02 , DOI: 10.1038/s41588-025-02205-2
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

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.



中文翻译:

系统发育推断揭示了循环肿瘤细胞簇中的克隆异质性

循环肿瘤细胞 (CTC) 簇是各种癌症中的高效转移种子。然而,它们的遗传异质性和克隆结构的表征很差。使用全外显子组测序结合来自乳腺癌和前列腺癌患者 CTC 簇的系统发育推断,以及小鼠癌症模型以及体内条形码介导的克隆追踪,我们展示了单个 CTC 簇的寡克隆组成。这些结果提高了我们对转移相关克隆动力学的理解。

更新日期:2025-06-03
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