ArticleCell genomics2022
Integration of multiple lineage measurements from the same cell reconstructs parallel tumor evolution.
Article in Cell genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Harnessing human tumor organoids for cancer modeling and precision therapy.Protein & cell · 2026Review
- Cell lineage tracing: Methods, applications, and challenges.Quantitative biology (Beijing, China) · 2025Review
- Isolation and tracing of matrix-producing notochordal and chondrocyte cells using ACAN-2A-mScarlet reporter human iPSC lines.Science advances · 2024Article
- Clonal tracking in cancer and metastasis.Cancer metastasis reviews · 2024Review
- High clonal diversity and spatial genetic admixture in early prostate cancer and surrounding normal tissue.Nature communications · 2024Article
- Single-cell lineage tracing with endogenous markers.Biophysical reviews · 2024Review
- Computational immunogenomic approaches to predict response to cancer immunotherapies.Nature reviews. Clinical oncology · 2024Review
- Modeling specific aneuploidies: from karyotype manipulations to biological insights.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Review
- Alliance of Heart and Endoderm: Multilineage Organoids to Model Co-development.Circulation research · 2023Review
- Chromosomal Instability, Selection and Competition: Factors That Shape the Level of Karyotype Intra-Tumor Heterogeneity.Cancers · 2022Review
- The eternal quest for self-improvement of somatic cells.Cell genomics · 2022Article
- Open questions in human lung organoid research.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Organoid evolution models complemented with integrated single-cell sequencing technology provide a powerful platform to characterize intra-tumor heterogeneity (ITH) and tumor evolution. Here, we conduct a parallel evolution experiment to mimic the tumor evolution process by evolving a colon cancer organoid model over 100 generations, spanning 6 months in time. We use single-cell whole-genome sequencing (WGS) in combination with viral lineage tracing at 12 time points to simultaneously monitor clone size, CNV states, SNV states, and viral lineage barcodes for 1,641 single cells. We integrate these measurements to construct clonal evolution trees with high resolution. We characterize the order of events in which chromosomal aberrations occur and identify aberrations that recur multiple times within the same tumor sub-population. We observe recurrent sequential loss of chromosome 4 after loss of chromosome 18 in four unique tumor clones. SNVs and CNVs identified in our organoid experiments are also frequently reported in colorectal carcinoma samples, and out of 334 patients with chromosome 18 loss in a Memorial Sloan Kettering colorectal cancer cohort, 99 (29.6%) also harbor chromosome 4 loss. Our study reconstructs tumor evolution in a colon cancer organoid model at high resolution, demonstrating an approach to identify potentially clinically relevant genomic aberrations in tumor evolution.
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