Small cell lung cancer tumors and preclinical models display heterogeneity of neuroendocrine phenotypes

Translational Lung Cancer Research
Wei ZhangAdi F Gazdar

Abstract

Small cell lung cancer (SCLC) is a deadly, high grade neuroendocrine (NE) tumor without recognized morphologic heterogeneity. However, over 30 years ago we described a SCLC subtype with "variant" morphology which did not express some NE markers and exhibited more aggressive growth. To quantitate NE properties of SCLCs, we developed a 50-gene expression-based NE score that could be applied to human SCLC tumors and cell lines, and genetically engineered mouse (GEM) models. We identified high and low NE subtypes of SCLC in all of our sample types, and characterized their properties. We found that 16% of human SCLC tumors and 10% of SCLC cell lines were of the low NE subtype, as well as cell lines from the GEM model. High NE SCLC lines grew as non-adherent floating aggregates or spheroids while Low NE lines had morphologic features of the variant subtype and grew as loosely attached cells. While the high NE subtype expressed one of the NE lineage master transcription factors ASCL1 or NEUROD1, together with NKX2-1, the entire range of NE markers, and lacked expression of the neuronal and NE repressor REST, the low NE subtype had lost expression of most NE markers, ASCL1, NEUROD1 and NKX2-1 and expressed REST. The low NE subtype had ...Continue Reading

Citations

Mar 23, 2019·Expert Review of Molecular Diagnostics·Giuseppe PelosiChristian H Ottensmeier
Feb 19, 2020·Expert Opinion on Therapeutic Targets·Jane S Y SuiSteven G Gray
Feb 10, 2019·The Journal of Experimental Medicine·Huanhuan J ChenHarold Varmus
Aug 18, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yuki TenjinTakaaki Ito
Mar 31, 2019·Nature Reviews. Cancer·Charles M RudinAdi F Gazdar
Jul 4, 2018·Genes & Development·Karine PozoJane E Johnson
Jul 21, 2019·Nature Communications·Xu-Dong WangYonghao Yu
Nov 28, 2020·Scientific Reports·Somayeh Layeghi-GhalehsoukhtehThomas M Wilkie
Aug 17, 2019·Cancer Discovery·Anna F FaragoBenjamin J Drapkin
Jan 22, 2021·Virchows Archiv : an International Journal of Pathology·Jasna MetovicGiuseppe Pelosi
Feb 5, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·John T PoirierTrudy G Oliver
Feb 20, 2021·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Win Sen HengFrank A E Kruyt
Mar 16, 2021·Molecular Therapy Oncolytics·Anna SchwendenweinBalazs Dome
Jun 10, 2020·Cold Spring Harbor Perspectives in Medicine·Benjamin J Drapkin, Charles M Rudin
Apr 4, 2021·Seminars in Diagnostic Pathology·Jasna MetovicGiuseppe Pelosi
Oct 5, 2020·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Marina K BaineNatasha Rekhtman
Apr 23, 2021·ESMO Open·P Martín-MartorellA Cervantes
May 21, 2021·Genes & Development·Justin P NortonDavid MacPherson
May 21, 2021·Genes & Development·Rachelle R OlsenTrudy G Oliver

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