{"doi":"10.1016/j.ccell.2024.05.003","title":"Olfactory neuroblastoma mimics molecular heterogeneity and lineage trajectories of small-cell lung cancer","abstract":"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.","journal":"Cancer Cell","year":2024,"id":420080,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9445,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":302443,"name":"Abbie S. Ireland","orcid":"0000-0002-4178-7239","position":1,"is_corresponding":false},{"id":1210892,"name":"Sarah B. Hawgood","orcid":"0009-0006-5983-8790","position":2,"is_corresponding":false},{"id":1211529,"name":"Tony Reyes","orcid":null,"position":3,"is_corresponding":false},{"id":844265,"name":"Tiffany Ko","orcid":"0000-0002-5006-6345","position":4,"is_corresponding":false},{"id":357500,"name":"Rachelle R. Olsen","orcid":null,"position":5,"is_corresponding":false},{"id":106316,"name":"Ralph Abi Hachem","orcid":"0009-0000-4007-8505","position":6,"is_corresponding":false},{"id":810297,"name":"David W. Jang","orcid":"0000-0003-4200-7174","position":7,"is_corresponding":false},{"id":497689,"name":"Diana Bell","orcid":"0000-0002-3531-8241","position":8,"is_corresponding":false},{"id":225134,"name":"Joseph M. Chan","orcid":"0000-0001-5249-7395","position":9,"is_corresponding":false},{"id":106319,"name":"Bradley J. Goldstein","orcid":"0000-0002-9612-1696","position":10,"is_corresponding":false},{"id":6196,"name":"Trudy G. Oliver","orcid":"0000-0003-2082-2397","position":11,"is_corresponding":false},{"id":448832,"name":"John B. Finlay","orcid":"0000-0002-3038-1276","position":0,"is_corresponding":true}],"reference_count":147,"raw_metadata":null,"created_at":"2026-07-19T01:57:25.777459Z","pmid":"38788720","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}