ArticleNature medicine2016
Pan-cancer analysis of the extent and consequences of intratumor heterogeneity.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 494 papers.
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Who cites it
494 citing papers in PubMed.
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- Subclonal TP53 mutations are frequent and predict resistance to radioimmunotherapy in follicular lymphoma.Blood advances · 2023Trial
- DCE-MRI kinetic heterogeneity facilitates the discrimination of benignity and malignancy of breast in combination with the DWI and morphological features.European journal of radiology open · 2026Article
- CDState Resolves Malignant Cell Heterogeneity from Bulk Tumor RNA Sequencing Data.Cancer research · 2026Article
- Genetic intratumour heterogeneity in digestive high-grade neuroendocrine neoplasms.Journal of neuroendocrinology · 2026Article
- Integrating Multimodal MRI Habitat and Transformer-Based Pathomics to Predict High-Risk Molecular Subtypes and Explore Biological Mechanisms in Adult Diffuse Gliomas.CNS neuroscience & therapeutics · 2026Article
- Review
- Bladder cancer precision-cut tumor slices (PCTS) preserve functional immune microenvironment enabling ex vivo drug evaluation.BMC medicine · 2026Article
- Development of a universal imaging "phenome" using shape, appearance and motion (SAM) features and the SAM Phenotype Observation Tool (SPOT).Nature communications · 2026Article
- Noninvasive Characterization of Tumor Heterogeneity in HNSCC: From Clinical Utility to Biological Correlates.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multi-regional transcriptomics reveals robust consensus subtypes beyond tumor heterogeneity of breast cancer.Translational oncology · 2026Article
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- Article
- Unraveling the Molecular Mechanisms Underlying Spontaneous Multipolar Mitosis Through CIN-seq.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Accurate detection of tumor clonality and ongoing expansion mode from genomic data.bioRxiv : the preprint server for biology · 2026Article
- Review
- A network-based deep learning model integrating subclonal architecture for therapy response prediction in cancer.Cell reports methods · 2026Article
- Plasticity, signaling, and metabolic rewiring in melanoma persister cells.Communications biology · 2026Review
- Variant allele frequency as a potential marker in response to frontline systemic therapy for patients with locally advanced and metastatic urothelial carcinoma.Translational andrology and urology · 2026Article
- Novel 4D radiomics applied to dynamic FES PET images to improve prediction of breast cancer response to ER-targeted therapy.European journal of nuclear medicine and molecular imaging · 2026Article
434 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
Abstract
Intratumor heterogeneity (ITH) drives neoplastic progression and therapeutic resistance. We used the bioinformatics tools 'expanding ploidy and allele frequency on nested subpopulations' (EXPANDS) and PyClone to detect clones that are present at a ≥10% frequency in 1,165 exome sequences from tumors in The Cancer Genome Atlas. 86% of tumors across 12 cancer types had at least two clones. ITH in the morphology of nuclei was associated with genetic ITH (Spearman's correlation coefficient, ρ = 0.24-0.41; P < 0.001). Mutation of a driver gene that typically appears in smaller clones was a survival risk factor (hazard ratio (HR) = 2.15, 95% confidence interval (CI): 1.71-2.69). The risk of mortality also increased when >2 clones coexisted in the same tumor sample (HR = 1.49, 95% CI: 1.20-1.87). In two independent data sets, copy-number alterations affecting either <25% or >75% of a tumor's genome predicted reduced risk (HR = 0.15, 95% CI: 0.08-0.29). Mortality risk also declined when >4 clones coexisted in the sample, suggesting a trade-off between the costs and benefits of genomic instability. ITH and genomic instability thus have the potential to be useful measures that can universally be applied to all cancers.
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