ArticleCancer prevention research (Philadelphia, Pa.)2011
Accurate reconstruction of the temporal order of mutations in neoplastic progression.
Article in Cancer prevention research (Philadelphia, Pa.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 62 citations in OpenAlex.
- Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.Pharmacological reviews · 2025Review
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- A phylogenetic approach to inferring the order in which mutations arise during cancer progression.PLoS computational biology · 2022Article
- Parsimonious Clone Tree Integration in cancer.Algorithms for molecular biology : AMB · 2022Article
- Deciphering the Increased Prevalence of TP53 Mutations in Metastatic Prostate Cancer.Cancer informatics · 2022Article
- Conditional prediction of consecutive tumor evolution using cancer progression models: What genotype comes next?PLoS computational biology · 2021Article
- Review
- Modelling bistable tumour population dynamics to design effective treatment strategies.Journal of theoretical biology · 2019Article
- Cancer progression models and fitness landscapes: a many-to-many relationship.Bioinformatics (Oxford, England) · 2018Article
- Precancer in ulcerative colitis: the role of the field effect and its clinical implications.Carcinogenesis · 2018Review
- A population genetics perspective on the determinants of intra-tumor heterogeneity.Biochimica et biophysica acta. Reviews on cancer · 2017Review
- The evolution of tumour phylogenetics: principles and practice.Nature reviews. Genetics · 2017Review
- Spatial Measures of Genetic Heterogeneity During Carcinogenesis.Bulletin of mathematical biology · 2017Article
- Quantifying the Dynamics of Field Cancerization in Tobacco-Related Head and Neck Cancer: A Multiscale Modeling Approach.Cancer research · 2016Article
- Research Needs for Understanding the Biology of Overdiagnosis in Cancer Screening.Journal of cellular physiology · 2016Review
- Identification of neutral tumor evolution across cancer types.Nature genetics · 2016Article
- FISHtrees 3.0: Tumor Phylogenetics Using a Ploidy Probe.PloS one · 2016Article
- The mathematics of cancer: integrating quantitative models.Nature reviews. Cancer · 2015Review
- Genetic Insights in Barrett's Esophagus and Esophageal Adenocarcinoma.Gastroenterology · 2015Review
- Genome-wide mutational spectra analysis reveals significant cancer-specific heterogeneity.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
The canonical route from normal tissue to cancer occurs through sequential acquisition of somatic mutations. Many studies have constructed a linear genetic model for tumorigenesis using the genetic alterations associated with samples at different stages of neoplastic progression from cross-sectional data. The common interpretation of these models is that they reflect the temporal order within any given tumor. Linear genetic methods implicitly neglect genetic heterogeneity within a neoplasm; each neoplasm is assumed to consist of one dominant clone. We modeled neoplastic progression of colorectal cancer using an agent-based model of a colon crypt and found clonal heterogeneity within our simulated neoplasms, as observed in vivo. Just 7.3% of cells within neoplasms acquired mutations in the same order as the linear model. In 41% of the simulated neoplasms, no cells acquired mutations in the same order as the linear model. We obtained similarly poor results when comparing the temporal order with oncogenetic tree models inferred from cross-sectional data. However, when we reconstructed the cell lineage of mutations within a neoplasm using several biopsies, we found that 99.7% cells within neoplasms acquired their mutations in an order consistent with the cell lineage mutational order. Thus, we find that using cross-sectional data to infer mutational order is misleading, whereas phylogenetic methods based on sampling intratumor heterogeneity accurately reconstructs the evolutionary history of tumors. In addition, we find evidence that disruption of differentiation is likely the first lesion in progression for most cancers and should be one of the few regularities of neoplastic progression across cancers.
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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.