ArticleProceedings of the National Academy of Sciences of the United States of America2016
Early and multiple origins of metastatic lineages within primary tumors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Intratumor Heterogeneity as a Prognostic Factor in Solid Tumors: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Clinical metastatic cancer from initiation to colonization: emerging challenges and breakthroughs.Oncogene · 2026Review
- Clonal evolution and mutational trajectories of metastatic colorectal cancer shaped by anticancer therapies.Nature communications · 2026Article
- Article
- The Pro-Metastatic Roles of ROS.Antioxidants (Basel, Switzerland) · 2026Review
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 2026Review
- Interpreting cancer genetics through a two-step "evolutionary cascade hypothesis": bridging neutral and selective perspectives.Journal of translational medicine · 2026Review
- Mutational landscape of normal breast tissues adjacent to invasive breast cancer.Cell reports. Medicine · 2026Article
- Evolutionary dynamics of early and late mutational signatures in metastatic cancer.Frontiers in bioinformatics · 2026Article
- Tracing metastatic spread in pediatric solid tumors using copy number and targeted deep sequencing.The Journal of pathology · 2025Article
- TyCHE enables time-resolved lineage tracing of heterogeneously-evolving populations.bioRxiv : the preprint server for biology · 2025Article
- Extrachromosomal DNA: shaping the evolutionary dynamics of cancer.Trends in cancer · 2025Review
- Circulating tumor cells: Blood-based detection, molecular biology, and clinical applications.Cancer cell · 2025Review
- Mutations in tumor signaling, metastases, and synthetic lethality establish distinct patterns.PLoS computational biology · 2025Article
- Proximate and ultimate causes of pregnancy sickness.Evolution, medicine, and public health · 2025Review
- Article
- Current biological implications and clinical relevance of metastatic circulating tumor cells.Clinical and experimental medicine · 2024Review
- The evolutionary theory of cancer: challenges and potential solutions.Nature reviews. Cancer · 2024Review
- Circulating tumor cells: from new biological insights to clinical practice.Signal transduction and targeted therapy · 2024Review
- How much do we know about the metastatic process?Clinical & experimental metastasis · 2024Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases.
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