系统发育推断揭示了循环肿瘤细胞簇中的克隆异质性。

Phylogenetic inference reveals clonal heterogeneity in circulating tumor cell clusters.

作者信息

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

机构信息

Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.

Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.

出版信息

Nat Genet. 2025 Jun 2. doi: 10.1038/s41588-025-02205-2.

DOI:10.1038/s41588-025-02205-2

PMID:40457073

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.

摘要

循环肿瘤细胞（CTC）簇是多种癌症中高效的转移种子。然而，它们的基因异质性和克隆结构却鲜有描述。通过对乳腺癌和前列腺癌患者的CTC簇进行全外显子测序并结合系统发育推断，以及利用小鼠癌症模型和体内条形码介导的克隆追踪，我们证明了单个CTC簇的寡克隆组成。这些结果增进了我们对与转移相关的克隆动态的理解。