ArticleGenome biology2016
Tracing the origin of disseminated tumor cells in breast cancer using single-cell sequencing.
Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 7 citations in OpenAlex.
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- Single-Cell Analysis of Bone-Marrow-Disseminated Tumour Cells.Diagnostics (Basel, Switzerland) · 2024Review
- Computational immunogenomic approaches to predict response to cancer immunotherapies.Nature reviews. Clinical oncology · 2024Review
- Microfluidic Isolation of Disseminated Tumor Cells from the Bone Marrow of Breast Cancer Patients.International journal of molecular sciences · 2023Article
- Testing for Phylogenetic Signal in Single-Cell RNA-Seq Data.Journal of computational biology : a journal of computational molecular cell biology · 2023Article
- Actin cytoskeleton depolymerization increases matrix metalloproteinase gene expression in breast cancer cells by promoting translocation of cysteine-rich protein 2 to the nucleus.Frontiers in cell and developmental biology · 2023Article
- Temporal and spatial characteristics of tumor evolution in a mouse model of oral squamous cell carcinoma.BMC cancer · 2022Article
- Multicellular immune dynamics implicate PIM1 as a potential therapeutic target for uveitis.Nature communications · 2022Article
- Leveraging single-cell sequencing to unravel intratumour heterogeneity and tumour evolution in human cancers.The Journal of pathology · 2022Review
- Intratumor genetic heterogeneity and clonal evolution to decode endometrial cancer progression.Oncogene · 2022Article
- Integration of multiple lineage measurements from the same cell reconstructs parallel tumor evolution.Cell genomics · 2022Article
- Mechanisms of breast cancer metastasis.Clinical & experimental metastasis · 2022Review
- Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity.Investigative ophthalmology & visual science · 2021Article
- Single-cell RNA sequencing reveals cell heterogeneity and transcriptome profile of breast cancer lymph node metastasis.Oncogenesis · 2021Article
- Circulating tumor cell detection and single-cell analysis using an integrated workflow based on ChimeraXMolecular oncology · 2021Article
- The Multifaceted Effects of Breast Cancer on Tumor-Draining Lymph Nodes.The American journal of pathology · 2021Review
- Colonization of distant organs by tumor cells generating circulating homotypic clusters adaptive to fluid shear stress.Scientific reports · 2021Article
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20 authors at 4 institutions in 4 countries.
Funding
Abstract
backgroundSingle-cell micro-metastases of solid tumors often occur in the bone marrow. These disseminated tumor cells (DTCs) may resist therapy and lay dormant or progress to cause overt bone and visceral metastases. The molecular nature of DTCs remains elusive, as well as when and from where in the tumor they originate. Here, we apply single-cell sequencing to identify and trace the origin of DTCs in breast cancer.
resultsWe sequence the genomes of 63 single cells isolated from six non-metastatic breast cancer patients. By comparing the cells' DNA copy number aberration (CNA) landscapes with those of the primary tumors and lymph node metastasis, we establish that 53% of the single cells morphologically classified as tumor cells are DTCs disseminating from the observed tumor. The remaining cells represent either non-aberrant "normal" cells or "aberrant cells of unknown origin" that have CNA landscapes discordant from the tumor. Further analyses suggest that the prevalence of aberrant cells of unknown origin is age-dependent and that at least a subset is hematopoietic in origin. Evolutionary reconstruction analysis of bulk tumor and DTC genomes enables ordering of CNA events in molecular pseudo-time and traced the origin of the DTCs to either the main tumor clone, primary tumor subclones, or subclones in an axillary lymph node metastasis.
conclusionsSingle-cell sequencing of bone marrow epithelial-like cells, in parallel with intra-tumor genetic heterogeneity profiling from bulk DNA, is a powerful approach to identify and study DTCs, yielding insight into metastatic processes. A heterogeneous population of CNA-positive cells is present in the bone marrow of non-metastatic breast cancer patients, only part of which are derived from the observed tumor lineages.
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