ArticlePLoS genetics2016
Integrated Multiregional Analysis Proposing a New Model of Colorectal Cancer Evolution.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 107 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinical utility and applicability of circulating tumor DNA testing in esophageal cancer: a systematic review and meta-analysis.Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus · 2022Pooled it
- Phase IB/II study of alpelisib combined with paclitaxel in patients with PIK3CA-altered metastatic or recurrent gastric cancer.The oncologist · 2026Trial
- Circulating DNA Demonstrates Convergent Evolution and Common Resistance Mechanisms during Treatment of Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Multiregion ultra-deep sequencing reveals early intermixing and variable levels of intratumoral heterogeneity in colorectal cancer.Molecular oncology · 2017Trial
- LeafRank: A phylodynamic framework for inferring relative fitness from single-cell phylogenies in chromosomally unstable tumors.bioRxiv : the preprint server for biology · 2026Article
- Recurrent mutations in protein tyrosine phosphatase receptor-type kappa in depressed-type colorectal carcinomas.Journal of biochemistry · 2026Article
- Identification of the novel therapeutic target gene SLC12A9, which determines the prognosis of patients with colorectal cancer.Surgery today · 2026Article
- Novel driver gene FIRRM regulates the cell cycle for promoting tumor growth in hepatocellular carcinoma.Journal of gastroenterology · 2026Article
- A Hallmark-Integrated, Agent-Based Framework for Intratumor Heterogeneity in Melanoma Evolution.Bulletin of mathematical biology · 2026Article
- PSMD12 Overexpression Promotes Lung Adenocarcinoma Progression via Ubiquitin-Proteasome Pathway Dysregulation.Cancer science · 2026Article
- ZNF282 Promotes Colorectal Cancer Progression Possibly via E2F1 Activation.Cancer science · 2026Article
- Early mutational events and clonal dynamics in normal crypts: implications for colorectal tumorigenesis.Human genomics · 2025Review
- Antibody-Protein L Functionalized Microparticles for Detection of Surface Markers in Heterogeneous Colorectal Lesions.bioRxiv : the preprint server for biology · 2025Article
- A set cover algorithm identifies minimal circulating tumour DNA sequencing targets for colorectal cancer detection.Scientific reports · 2025Article
- Polarity Gene PARD6B Promotes Tumor Growth of Colorectal Cancer via Increasing MYC Expression.Cancer science · 2025Article
- SEC61G promotes colorectal cancer progression by regulating cytosolic CaJournal of gastroenterology · 2025Article
- Asymmetric cell division of ALDH1-positive cancer stem cells generates glycolytic metabolically diverse cell populations.Scientific reports · 2025Article
- Evidence of DNA methylation heterogeneity and epipolymorphism in kidney cancer tissue samples.Oncogene · 2025Article
- Spatial deconvolution from bulk DNA methylation profiles determines intratumoral epigenetic heterogeneity.Cell & bioscience · 2025Article
- Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
41 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding intratumor heterogeneity is clinically important because it could cause therapeutic failure by fostering evolutionary adaptation. To this end, we profiled the genome and epigenome in multiple regions within each of nine colorectal tumors. Extensive intertumor heterogeneity is observed, from which we inferred the evolutionary history of the tumors. First, clonally shared alterations appeared, in which C>T transitions at CpG site and CpG island hypermethylation were relatively enriched. Correlation between mutation counts and patients' ages suggests that the early-acquired alterations resulted from aging. In the late phase, a parental clone was branched into numerous subclones. Known driver alterations were observed frequently in the early-acquired alterations, but rarely in the late-acquired alterations. Consistently, our computational simulation of the branching evolution suggests that extensive intratumor heterogeneity could be generated by neutral evolution. Collectively, we propose a new model of colorectal cancer evolution, which is useful for understanding and confronting this heterogeneous disease.
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Registered trials
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.