Phylogenetic inference reveals clonal heterogeneity in circulating tumor cell clusters

IF 31.7 1区生物学 Q1 GENETICS & HEREDITY

Nature genetics 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

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Abstract

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. Phylogenetic analyses in patients with cancer and xenograft models highlight heterogeneity within individual CTC clusters, providing insights into clonal dynamics during metastasis.

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系统发育推断揭示了循环肿瘤细胞群的克隆异质性

循环肿瘤细胞（CTC）簇是多种肿瘤高效转移的种子。然而，它们的遗传异质性和克隆结构却没有得到很好的表征。利用全外显子组测序，结合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条形码介导的体内克隆跟踪，我们证明了单个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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature genetics 生物-遗传学

CiteScore

43.00

自引率

2.60%

发文量

241

审稿时长

3 months

期刊介绍： Nature Genetics publishes the very highest quality research in genetics. It encompasses genetic and functional genomic studies on human and plant traits and on other model organisms. Current emphasis is on the genetic basis for common and complex diseases and on the functional mechanism, architecture and evolution of gene networks, studied by experimental perturbation. Integrative genetic topics comprise, but are not limited to: -Genes in the pathology of human disease -Molecular analysis of simple and complex genetic traits -Cancer genetics -Agricultural genomics -Developmental genetics -Regulatory variation in gene expression -Strategies and technologies for extracting function from genomic data -Pharmacological genomics -Genome evolution