ArticleCancer discovery2023
Extrachromosomal DNA Amplification Contributes to Small Cell Lung Cancer Heterogeneity and Is Associated with Worse Outcomes.
Article in Cancer discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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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
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Who cites it
85 citing papers in PubMed, 109 citations in OpenAlex.
- Plasma nucleosome profiling reports on tumor burden and molecular subtypes in small cell lung cancer.The Journal of clinical investigation · 2026Article
- Extrachromosomal Circular DNA May Contribute to Histopathologic Characteristics in Esophageal Combined Basaloid Squamous Cell Carcinoma.Annals of surgical oncology · 2026Article
- Extrachromosomal DNA as a platform for epigenetic reprogramming in cancer.Molecular cancer · 2026Review
- Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.Biomarker research · 2026Review
- Multi-omics profiling of recurrence-associated extrachromosomal circular DNA characteristics and its prognostic potential in lung adenocarcinoma.Precision clinical medicine · 2026Article
- Extrachromosomal DNA in urothelial carcinoma: mechanisms and clinical applications.Nature reviews. Urology · 2026Review
- Spindle Assembly Checkpoint Competency Determines Sensitivity to KIF18A Inhibition in Small Cell Lung Cancer.Cancer research communications · 2026Article
- Advancing the applications of liquid biopsies in oncology.Nature reviews. Genetics · 2026Review
- Blockade of Tumor-Intrinsic TGFβ Signaling Drives Hyperprogression in Small Cell Lung Cancer.Cancer discovery · 2026Article
- MYC in Oncogenesis and Therapeutic Implications.MedComm · 2026Review
- Proteomic Profiling Identifies CLDN3 as a Tumor-Selective Therapeutic Target in Small Cell Lung Cancer.bioRxiv : the preprint server for biology · 2026Article
- Exploring copy number alterations (CNAs) to gain new insight into SCLC heterogeneity.Molecular biology reports · 2026Review
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- Beyond chromosomes: exploring the diverse functions of extrachromosomal circular DNA.Journal of advanced research · 2026Review
- Extrachromosomal DNA Amplification as a Prognostic Factor for Cancer.Journal of personalized medicine · 2026Review
- Replication origin flexibility: a tool to mitigate the hazards of excess replication.Trends in genetics : TIG · 2026Review
- Esophageal neuroendocrine carcinoma: molecular insights, diagnostic advances, and emerging treatment strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- The Impact of Targeting TRAF2 and NCK-Interacting Protein Kinase on Antitumor Effect and Tumor Immune Environment in c-MYC-High SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- The newfound relationship between extrachromosomal DNAs and excised signal circles.FEBS letters · 2026Review
- Extrachromosomal DNA Gives Cancer a New Evolutionary Pathway.Research square · 2026Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors at 6 institutions in 4 countries.
Funding
Abstract
Small-cell lung cancer (SCLC) is an aggressive neuroendocrine lung cancer. Oncogenic MYC amplifications drive SCLC heterogeneity, but the genetic mechanisms of MYC amplification and phenotypic plasticity, characterized by neuroendocrine and nonneuroendocrine cell states, are not known. Here, we integrate whole-genome sequencing, long-range optical mapping, single-cell DNA sequencing, and fluorescence in situ hybridization to find extrachromosomal DNA (ecDNA) as a primary source of SCLC oncogene amplifications and driver fusions. ecDNAs bring to proximity enhancer elements and oncogenes, creating SCLC transcription-amplifying units, driving exceptionally high MYC gene dosage. We demonstrate that cell-free nucleosome profiling can noninvasively detect ecDNA amplifications in plasma, facilitating its genome-wide interrogation in SCLC and other cancers. Altogether, our work provides the first comprehensive map of SCLC ecDNA and describes a new mechanism that governs MYC-driven SCLC heterogeneity. ecDNA-enabled transcriptional flexibility may explain the significantly worse survival outcomes of SCLC harboring complex ecDNA amplifications. SIGNIFICANCE: MYC drives SCLC progression, but the genetic basis of MYC-driven SCLC evolution is unknown. Using SCLC as a paradigm, we report how ecDNA amplifications function as MYC-amplifying units, fostering tumor plasticity and a high degree of tumor heterogeneity. This article is highlighted in the In This Issue feature, p. 799.
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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.