ArticleThe Journal of clinical investigation2010
Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers.
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Who cites it
209 citing papers in PubMed.
- Trial
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- Fraternal cooperation of hierarchical cancer parallels metazoan multicellularity and eusociality.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Integrating trajectory inference and self-explainable predictive models to explore cell state transitions in breast cancer at single-cell resolution.Frontiers in bioinformatics · 2026Article
- Predicting response to neoadjuvant chemotherapy in muscle-invasive bladder cancer via interpretable multimodal deep learning.NPJ digital medicine · 2025Article
- The Spiral Model of Evolution: Stable Life Forms of Organisms and Unstable Life Forms of Cancers.International journal of molecular sciences · 2024Review
- Heterogeneous Evolution of Breast Cancer Cells-An Endogenous Molecular-Cellular Network Study.Biology · 2024Article
- Spatial Biology of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2024Review
- Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance.Signal transduction and targeted therapy · 2024Review
- Identifying the effectiveness of 3D culture systems to recapitulate breast tumor tissue in situ.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Decoding the basis of histological variation in human cancer.Nature reviews. Cancer · 2024Review
- Diagnostic challenges in complicated case of glioblastoma.Pathology oncology research : POR · 2024Article
- Single-cell transcriptomic analysis of gingivo-buccal oral cancer reveals two dominant cellular programs.Cancer science · 2023Article
- A multiscale model of the role of microenvironmental factors in cell segregation and heterogeneity in breast cancer development.PLoS computational biology · 2023Article
- Using picoliter droplet deposition to track clonal competition in adherent and organoid cancer cell cultures.Scientific reports · 2023Article
- FunSpace: A functional and spatial analytic approach to cell imaging data using entropy measures.PLoS computational biology · 2023Article
- Cell Cycle Status Influences Resistance to Apoptosis Induced by Oxidative Stress in Human Breast Cancer Cells, Which Is Accompanied by Modulation of Autophagy.Current issues in molecular biology · 2023Article
- Patient-derived three-dimensional culture techniques model tumor heterogeneity in head and neck cancer.Oral oncology · 2023Review
149 more citing papers are in PubMed but not listed here.
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5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Intratumor genetic heterogeneity is a key mechanism underlying tumor progression and therapeutic resistance. The prevailing model for explaining intratumor diversity, the clonal evolution model, has recently been challenged by proponents of the cancer stem cell hypothesis. To investigate this issue, we performed combined analyses of markers associated with cellular differentiation states and genotypic alterations in human breast carcinomas and evaluated diversity with ecological and evolutionary methods. Our analyses showed a high degree of genetic heterogeneity both within and between distinct tumor cell populations that were defined based on markers of cellular phenotypes including stem cell-like characteristics. In several tumors, stem cell-like and more-differentiated cancer cell populations were genetically distinct, leading us to question the validity of a simple differentiation hierarchy-based cancer stem cell model. The degree of diversity correlated with clinically relevant breast tumor subtypes and in some tumors was markedly different between the in situ and invasive cell populations. We also found that diversity measures were associated with clinical variables. Our findings highlight the importance of genetic diversity in intratumor heterogeneity and the value of analyzing tumors as distinct populations of cancer cells to more effectively plan treatments.
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