دورية أكاديمية
Olfactory neuroblastoma mimics molecular heterogeneity and lineage trajectories of small-cell lung cancer.
العنوان: | Olfactory neuroblastoma mimics molecular heterogeneity and lineage trajectories of small-cell lung cancer. |
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المؤلفون: | Finlay JB; Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham 27710, NC, USA., Ireland AS; Department of Pharmacology and Cancer Biology, Duke University, Durham 27710, NC, USA., Hawgood SB; Department of Pharmacology and Cancer Biology, Duke University, Durham 27710, NC, USA., Reyes T; Department of Pharmacology and Cancer Biology, Duke University, Durham 27710, NC, USA; Department of Oncological Sciences, University of Utah, Salt Lake City 84112, UT, USA., Ko T; Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham 27710, NC, USA., Olsen RR; Department of Oncological Sciences, University of Utah, Salt Lake City 84112, UT, USA., Abi Hachem R; Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham 27710, NC, USA., Jang DW; Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham 27710, NC, USA., Bell D; Division of Anatomic Pathology, City of Hope Comprehensive Cancer Center, Duarte 91010, CA, USA., Chan JM; Human Oncology and Pathogenesis Program, Memorial-Sloan Kettering Cancer Center, New York City 10065, NY, USA., Goldstein BJ; Department of Head and Neck Surgery & Communication Sciences, Duke University, Durham 27710, NC, USA; Department of Neurobiology, Duke University, Durham 27710, NC, USA. Electronic address: bradley.goldstein@duke.edu., Oliver TG; Department of Pharmacology and Cancer Biology, Duke University, Durham 27710, NC, USA; Department of Oncological Sciences, University of Utah, Salt Lake City 84112, UT, USA. Electronic address: tgo@duke.edu. |
المصدر: | Cancer cell [Cancer Cell] 2024 Jun 10; Vol. 42 (6), pp. 1086-1105.e13. Date of Electronic Publication: 2024 May 23. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2002- |
مواضيع طبية MeSH: | Small Cell Lung Carcinoma*/genetics , Small Cell Lung Carcinoma*/pathology , Small Cell Lung Carcinoma*/metabolism , Esthesioneuroblastoma, Olfactory*/genetics , Esthesioneuroblastoma, Olfactory*/pathology , Cell Lineage* , Lung Neoplasms*/genetics , Lung Neoplasms*/pathology, Animals ; Mice ; Humans ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Tumor Microenvironment ; Nose Neoplasms/genetics ; Nose Neoplasms/pathology ; Olfactory Mucosa/pathology ; Olfactory Mucosa/metabolism ; Disease Models, Animal ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism |
مستخلص: | The olfactory epithelium undergoes neuronal regeneration from basal stem cells and is susceptible to olfactory neuroblastoma (ONB), a rare tumor of unclear origins. Employing alterations in Rb1/Trp53/Myc (RPM), we establish a genetically engineered mouse model of high-grade metastatic ONB exhibiting a NEUROD1 + immature neuronal phenotype. We demonstrate that globose basal cells (GBCs) are a permissive cell of origin for ONB and that ONBs exhibit cell fate heterogeneity that mimics normal GBC developmental trajectories. ASCL1 loss in RPM ONB leads to emergence of non-neuronal histopathologies, including a POU2F3 + microvillar-like state. Similar to small-cell lung cancer (SCLC), mouse and human ONBs exhibit mutually exclusive NEUROD1 and POU2F3-like states, an immune-cold tumor microenvironment, intratumoral cell fate heterogeneity comprising neuronal and non-neuronal lineages, and cell fate plasticity-evidenced by barcode-based lineage tracing and single-cell transcriptomics. Collectively, our findings highlight conserved similarities between ONB and neuroendocrine tumors with significant implications for ONB classification and treatment. Competing Interests: Declaration of interests TGO has a patent related to SCLC subtypes and a sponsored research agreement with Auron Therapeutics, serves on the scientific advisory board (SAB) for Lung Cancer Research Foundation, and as a consulting editor for Cancer Research and Genes & Development. BJG has interest in Rhino Therapeutics and is on the SAB for Smell and Taste Association of North America. J.C. has equity in Mirati Therapeutics and provision of services for Sonata Therapeutics. D.J. has consulted for Regeneron and ST Stent. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.) |
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معلومات مُعتمدة: | R01 DC016859 United States DC NIDCD NIH HHS; U24 CA213274 United States CA NCI NIH HHS; U01 CA231844 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; F31 CA275295 United States CA NCI NIH HHS; F30 DC021348 United States DC NIDCD NIH HHS; P30 CA014236 United States CA NCI NIH HHS; UM1 CA239755 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: ASCL1; NEUROD1; POU2F3; RPM; SCLC; esthesioneuroblastoma; neuroendocrine; olfactory neuroblastoma; plasticity; tuft |
المشرفين على المادة: | 0 (Basic Helix-Loop-Helix Transcription Factors) 0 (Ascl1 protein, mouse) 0 (ASCL1 protein, human) 0 (Tumor Suppressor Protein p53) |
تواريخ الأحداث: | Date Created: 20240524 Date Completed: 20240611 Latest Revision: 20240801 |
رمز التحديث: | 20240801 |
مُعرف محوري في PubMed: | PMC11186085 |
DOI: | 10.1016/j.ccell.2024.05.003 |
PMID: | 38788720 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1878-3686 |
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DOI: | 10.1016/j.ccell.2024.05.003 |