ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2019
Gene Expression Profiling of Lung Atypical Carcinoids and Large Cell Neuroendocrine Carcinomas Identifies Three Transcriptomic Subtypes with Specific Genomic Alterations.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Utility of KI-67 as a prognostic biomarker in pulmonary neuroendocrine neoplasms: a systematic review and meta-analysis.BMJ open · 2022Pooled it
- Identification of Actionable Gene Variants in Pulmonary Large-Cell Neuroendocrine Carcinoma: A Real-World Analysis of a Polish Cohort.International journal of molecular sciences · 2026Article
- Molecular alterations in high-grade neuroendocrine tumors of the small intestine.The Journal of pathology · 2026Article
- 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
- Digital Immunophenotyping of Lung Atypical Carcinoids and Large Cell Neuroendocrine Carcinomas Identifies Three Subtypes With Specific Tumor-Immune Microenvironment Features.Endocrine pathology · 2025Article
- Expression of YAP1 delineates distinct subtypes of pulmonary large cell neuroendocrine carcinoma with divergent therapeutic implications.Translational lung cancer research · 2025Article
- Review
- Genetic insight into lung neuroendocrine tumors: Notch and Wnt signaling pathways as potential targets.Journal of translational medicine · 2025Article
- Diagnostic relevance of p53 and Rb status in neuroendocrine tumors G3 from different organs: an immunohistochemical study of 465 high-grade neuroendocrine neoplasms.Virchows Archiv : an international journal of pathology · 2025Article
- Basic science and translational implications of current knowledge on neuroendocrine tumors.The Journal of clinical investigation · 2025Review
- Menin in Cancer.Genes · 2024Review
- The Genetic Analysis and Clinical Therapy in Lung Cancer: Current Advances and Future Directions.Cancers · 2024Review
- Role of Bone Metastases in Lung Neuroendocrine Neoplasms: Clinical Presentation, Treatment and Impact on Prognosis.International journal of molecular sciences · 2024Article
- Molecular Classification of Gastrointestinal and Pancreatic Neuroendocrine Neoplasms: Are We Ready for That?Endocrine pathology · 2024Review
- Advances in genetic profile and therapeutic strategy of pulmonary large cell neuroendocrine carcinoma.Frontiers in medicine · 2024Review
- Clinical characteristics and treatment management of combined large cell neuroendocrine carcinoma, a subtype of large cell neuroendocrine carcinoma.Frontiers in oncology · 2024Review
- Altered splicing machinery in lung carcinoids unveils NOVA1, PRPF8 and SRSF10 as novel candidates to understand tumor biology and expand biomarker discovery.Journal of translational medicine · 2023Article
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionDNA mutational profiling showed that atypical carcinoids (ACs) share alterations with large cell neuroendocrine carcinomas (LCNECs). Transcriptomic studies suggested that LCNECs are composed of two subtypes, one of which shares molecular anomalies with SCLC. The missing piece of information is the transcriptomic relationship between ACs and LCNECs, as a direct comparison is lacking in the literature.
methodsTranscriptomic and genomic alterations were investigated by next-generation sequencing in a discovery set of 14 ACs and 14 LCNECs and validated on 21 ACs and 18 LCNECs by using custom gene panels and immunohistochemistry for Men1 and Rb1.
resultsA 58-gene signature distinguished three transcriptional clusters. Cluster 1 comprised 20 LCNECs and one AC harboring concurrent inactivation of tumor protein p53 gene (TP53) and retinoblastoma 1 gene (RB1) in the absence of menin 1 gene (MEN1) mutations; all cases lacked Rb1 nuclear immunostaining. Cluster 3 included 20 ACs and four LCNECs lacking RB1 alterations and having frequent MEN1 (37.5%) and TP53 mutations (16.7%); menin nuclear immunostaining was lost in 75% of cases. Cluster 2 included 14 ACs and eight LCNECs showing intermediate features: TP53, 40.9%; MEN1, 22.7%; and RB1, 18.2%. Patients in cluster C1 had a shorter cancer-specific survival than did patients in C2 or C3.
conclusionsACs and LCNECs comprise three different and clinically relevant molecular diseases, one AC-enriched group in which MEN1 inactivation plays a major role, one LCNEC-enriched group whose hallmark is RB1 inactivation, and one mixed group with intermediate molecular features. These data support a progression of malignancy that may be traced by using combined molecular and immunohistochemical analysis.
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