ArticleCancer discovery2025
Chromothripsis-Mediated Small Cell Lung Carcinoma.
Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- What's new in neoplastic pulmonary pathology 2026: updates on grading, staging and molecular testing.Journal of pathology and translational medicine · 2026Article
- Deep molecular profiling of lung neuroendocrine tumours and supra-carcinoids.Molecular cancer · 2026Article
- Precision de-escalation of immunotherapy in extensive-stage small cell lung cancer: a case report on ctDNA-guided management in a long-term survivor.Translational cancer research · 2026Article
- Transcriptional evidence of neuroendocrine cell plasticity beyond histological boundaries in lung neuroendocrine neoplasms: an in-silico analysis suggesting a progression model.Journal of experimental & clinical cancer research : CR · 2026Article
- Clinically actionable molecular alterations in Rb-retained small cell lung carcinoma variants.Virchows Archiv : an international journal of pathology · 2026Article
- Successful Tarlatamab Rechallenge After Recurrent High-Grade Cytokine Release Syndrome in Chromothripsis-Mediated SCLC: A Case Report.JTO clinical and research reports · 2026Article
- Pancoast Syndrome and Middle Ear Mass as the First Manifestation of Small-Cell Lung Carcinoma: A Case Report.Clinical case reports · 2026Article
- European Society of Neuroendocrine Tumors (ENETS) 2025 guidance paper for lung and thymic carcinoids.Journal of neuroendocrinology · 2026Article
- Microplastics as environmental modifiers of lung disease.EMBO molecular medicine · 2026Review
- Targeting FOXM1 reshapes antitumor immunity to attenuate small cell lung cancer progression.Cancer letters · 2026Article
- ALK-rearranged lung adenocarcinoma transforming to mucoepidermoid carcinoma in a 45-year-old female: a case report.AME case reports · 2026Article
- Novel concepts of cell-of origin in neuroendocrine neoplasms.Virchows Archiv : an international journal of pathology · 2026Review
- Immunotherapy and the novel therapeutic development for small-cell lung cancer.Therapeutic advances in medical oncology · 2026Review
- Evidence for the transformation of a subset of pulmonary carcinoids to small cell lung carcinomas through shared molecular alterations.Frontiers in oncology · 2026Article
- Concept of neuroendocrine neoplasms of all organs with a focus on grading, subtyping.Virchows Archiv : an international journal of pathology · 2026Review
- Clinical utility of molecular profiling in rare lung neuroendocrine neoplasms.Frontiers in oncology · 2026Review
- Controversies in NEN: An ENETS position statement on the treatment of patients with Grade 3 well-differentiated neuroendocrine tumours of the gastro-enteropancreatic tract.Journal of neuroendocrinology · 2025Review
- Integrated circulating tumor DNA-based prognostic algorithm for limited stage small-cell lung cancer under definitive chemoradiotherapy and utility in consolidation immunotherapy benefit prediction.Cell communication and signaling : CCS · 2025Article
- Immunotherapy for small cell lung cancer: current challenges and prospects.Experimental hematology & oncology · 2025Review
- Learning the cellular origins across cancers using single-cell chromatin landscapes.Nature communications · 2025Article
Corrections and comments
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Authors and funding
42 authors.
Funding
Abstract
Small cell lung carcinoma (SCLC) is a highly aggressive malignancy that is typically associated with tobacco exposure and inactivation of RB1 and TP53 genes. Here, we performed detailed clinicopathologic, genomic, and transcriptomic profiling of an atypical subset of SCLC that lacked RB1 and TP53 co-inactivation and arose in never/light smokers. We found that most cases were associated with chromothripsis-massive, localized chromosome shattering-recurrently involving chromosome 11 or 12 and resulting in extrachromosomal amplification of CCND1 or co-amplification of CCND2/CDK4/MDM2, respectively. Uniquely, these clinically aggressive tumors exhibited genomic and pathologic links to pulmonary carcinoids, suggesting a previously uncharacterized mode of SCLC pathogenesis via transformation from lower-grade neuroendocrine tumors or their progenitors. Conversely, SCLC in never-smokers harboring inactivated RB1 and TP53 exhibited hallmarks of adenocarcinoma-to-SCLC derivation, supporting two distinct pathways of plasticity-mediated pathogenesis of SCLC in never-smokers. Significance: Here, we provide the first detailed description of a unique SCLC subset lacking RB1/TP53 alterations and identify extensive chromothripsis and pathogenetic links to pulmonary carcinoids as its hallmark features. This work defines atypical SCLC as a novel entity among lung cancers, highlighting its exceptional histogenesis, clinicopathologic characteristics, and therapeutic vulnerabilities. See related commentary by Nadeem and Drapkin, p. 8.
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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.