Observational studyScience translational medicine2015
Clonal status of actionable driver events and the timing of mutational processes in cancer evolution.
Observational study in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 411 papers.
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.
The trial behind it
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
411 citing papers in PubMed, 707 citations in OpenAlex.
- Lutetium-177-PSMA-617 or cabazitaxel in metastatic prostate cancer: circulating tumor DNA analysis of the randomized phase 2 TheraP trial.Nature medicine · 2025Trial
- Genomic signatures define three subtypes of EGFR-mutant stage II-III non-small-cell lung cancer with distinct adjuvant therapy outcomes.Nature communications · 2021Trial
- Phase 2 study of TAS-117, an allosteric akt inhibitor in advanced solid tumors harboring phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog gene mutations.Investigational new drugs · 2021Trial
- Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity.Nature communications · 2021Trial
- Prospective high-throughput genome profiling of advanced cancers: results of the PERMED-01 clinical trial.Genome medicine · 2021Trial
- Genetic intratumour heterogeneity in digestive high-grade neuroendocrine neoplasms.Journal of neuroendocrinology · 2026Article
- Genomic Characterization of RTK-RAS Pathway Alterations in Juvenile Myelomonocytic Leukemia Through Whole-Exome Sequencing.Medical sciences (Basel, Switzerland) · 2026Article
- Identification of novel paracrine therapeutic targets in peritoneal metastases through integrative proteotranscriptomic analysis of ascites.Molecular cancer · 2026Article
- Review
- [Variant Allele Frequency Stratification and EGFR Co-mutation Characteristics in AKT1 E17K-mutant Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Article
- Germline predisposition and somatic mutational landscape in synchronous mucinous metaplasia and neoplasia of the female genital tract.Clinical and translational medicine · 2026Article
- ITHindex: An integrated web-based platform for intratumor heterogeneity evaluation.PLOS digital health · 2026Article
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Convergence for Inactivation of TGFβ Signaling Is a Common Feature of Advanced Pancreatic Cancer.Cancer discovery · 2026Article
- Enhanced measures of neoantigenicity capture unique tumor-immune interactions across primary melanoma subtypes.Genome medicine · 2026Article
- Beyond Darwin: reactive heredity, burst-drift dynamics and eco‑evolutionary control of cancer.Molecular cancer · 2026Review
- Article
- Spatial tumor evolution panorama of ovarian cancer.Cell reports. Medicine · 2026Article
- Diverse genomic and transcriptomic heterogeneity in EGFR-mutant lung adenocarcinoma between exon 19 del and exon 21 L858R.Cell communication and signaling : CCS · 2026Article
- In-depth Genetic and Molecular Characterization of Unilateral Coexisting Adrenal Cortical Adenoma and Carcinoma in the Context of MEN1 Syndrome.Endocrine pathology · 2026Article
351 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Deciphering whether actionable driver mutations are found in all or a subset of tumor cells will likely be required to improve drug development and precision medicine strategies. We analyzed nine cancer types to determine the subclonal frequencies of driver events, to time mutational processes during cancer evolution, and to identify drivers of subclonal expansions. Although mutations in known driver genes typically occurred early in cancer evolution, we also identified later subclonal "actionable" mutations, including BRAF (V600E), IDH1 (R132H), PIK3CA (E545K), EGFR (L858R), and KRAS (G12D), which may compromise the efficacy of targeted therapy approaches. More than 20% of IDH1 mutations in glioblastomas, and 15% of mutations in genes in the PI3K (phosphatidylinositol 3-kinase)-AKT-mTOR (mammalian target of rapamycin) signaling axis across all tumor types were subclonal. Mutations in the RAS-MEK (mitogen-activated protein kinase kinase) signaling axis were less likely to be subclonal than mutations in genes associated with PI3K-AKT-mTOR signaling. Analysis of late mutations revealed a link between APOBEC-mediated mutagenesis and the acquisition of subclonal driver mutations and uncovered putative cancer genes involved in subclonal expansions, including CTNNA2 and ATXN1. Our results provide a pan-cancer census of driver events within the context of intratumor heterogeneity and reveal patterns of tumor evolution across cancers. The frequent presence of subclonal driver mutations suggests the need to stratify targeted therapy response according to the proportion of tumor cells in which the driver is identified.
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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.