ArticleCancer research2013
Single-molecule genomic data delineate patient-specific tumor profiles and cancer stem cell organization.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed.
- Fluctuating DNA methylation sites encode colorectal tumour growth history.bioRxiv : the preprint server for biology · 2026Article
- Advances in Colorectal Cancer Cell Biology and Clonal Evolution.International journal of molecular sciences · 2026Review
- Spatially Discontinuous Mutation Topographies in Ductal Carcinoma In Situ Reveal Noncompetitive Growth Dynamics.Cancer research · 2025Article
- Resolving tumor evolution: a phylogenetic approach.Journal of the National Cancer Center · 2024Review
- Tumour Growth Mechanisms Determine Effectiveness of Adaptive Therapy in Glandular Tumours.Interdisciplinary sciences, computational life sciences · 2024Article
- Growth Dynamics of Ductal Carcinoma in Situ Recapitulate Normal Breast Development.bioRxiv : the preprint server for biology · 2023Article
- Elements and evolutionary determinants of genomic divergence between paired primary and metastatic tumors.PLoS computational biology · 2021Article
- A mesoscopic simulator to uncover heterogeneity and evolutionary dynamics in tumors.PLoS computational biology · 2021Article
- Integrating genetic and non-genetic determinants of cancer evolution by single-cell multi-omics.Nature reviews. Genetics · 2021Review
- tugHall: a simulator of cancer-cell evolution based on the hallmarks of cancer and tumor-related genes.Bioinformatics (Oxford, England) · 2020Article
- Why is cancer not more common? A changing microenvironment may help to explain why, and suggests strategies for anti-cancer therapy.Open biology · 2020Article
- Mapping the breast cancer metastatic cascade onto ctDNA using genetic and epigenetic clonal tracking.Nature communications · 2020Article
- Modeling methylation dynamics with simultaneous changes in CpG islands.BMC bioinformatics · 2020Article
- Quantitative evidence for early metastatic seeding in colorectal cancer.Nature genetics · 2019Article
- Stem cells in homeostasis and cancer of the gut.Molecular cancer · 2019Review
- Searching for the needle in the haystack: deconvoluting the evolutionary dynamics of residual disease in human glioblastoma.Annals of oncology : official journal of the European Society for Medical Oncology · 2019Article
- Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy.Nature communications · 2019Article
- Spatial mutation patterns as markers of early colorectal tumor cell mobility.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Big Bang Tumor Growth and Clonal Evolution.Cold Spring Harbor perspectives in medicine · 2018Review
- Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Substantial evidence supports the concept that cancers are organized in a cellular hierarchy with cancer stem cells (CSC) at the apex. To date, the primary evidence for CSCs derives from transplantation assays, which have known limitations. In particular, they are unable to report on the fate of cells within the original human tumor. Because of the difficulty in measuring tumor characteristics in patients, cellular organization and other aspects of cancer dynamics have not been quantified directly, although they likely play a fundamental role in tumor progression and therapy response. As such, new approaches to study CSCs in patient-derived tumor specimens are needed. In this study, we exploited ultradeep single-molecule genomic data derived from multiple microdissected colorectal cancer glands per tumor, along with a novel quantitative approach to measure tumor characteristics, define patient-specific tumor profiles, and infer tumor ancestral trees. We show that each cancer is unique in terms of its cellular organization, molecular heterogeneity, time from malignant transformation, and rate of mutation and apoptosis. Importantly, we estimate CSC fractions between 0.5% and 4%, indicative of a hierarchical organization responsible for long-lived CSC lineages, with variable rates of symmetric cell division. We also observed extensive molecular heterogeneity, both between and within individual cancer glands, suggesting a complex hierarchy of mitotic clones. Our framework enables the measurement of clinically relevant patient-specific characteristics in vivo, providing insight into the cellular organization and dynamics of tumor growth, with implications for personalized patient care.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.