1. SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures
- Author
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Robin Sebastian, Nitin Roper, John D. Minna, Julia Krushkal, Mirit I. Aladjem, Paul S. Meltzer, Luc Girard, Camille Tlemsani, Sudhir Varma, Beverly A. Teicher, Fathi Elloumi, Lorinc Pongor, Augustin Luna, Kenneth E. Huffman, William C. Reinhold, Kurt W. Kohn, Anish Thomas, Vinodh N. Rajapakse, and Yves Pommier
- Subjects
Epigenomics ,0301 basic medicine ,Epithelial-Mesenchymal Transition ,Lung Neoplasms ,SLFN11 ,Notch signaling pathway ,Genomics ,Computational biology ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Epigenesis, Genetic ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,genomics ,Data Mining ,Humans ,Pharmacological and Toxicological Phenomena ,Schlafen ,native immune response ,Transcription factor ,neoplasms ,lcsh:QH301-705.5 ,PI3K/AKT/mTOR pathway ,YAP1 ,Reproducibility of Results ,DNA Methylation ,immune checkpoints ,Small Cell Lung Carcinoma ,respiratory tract diseases ,Gene Expression Regulation, Neoplastic ,ASCL1 ,030104 developmental biology ,lcsh:Biology (General) ,DNA methylation ,Algorithms ,Software ,030217 neurology & neurosurgery ,Transcription Factors ,STING - Abstract
SUMMARY CellMiner-SCLC (https://discover.nci.nih.gov/SclcCellMinerCDB/) integrates drug sensitivity and genomic data, including high-resolution methylome and transcriptome from 118 patient-derived small cell lung cancer (SCLC) cell lines, providing a resource for research into this “recalcitrant cancer.” We demonstrate the reproducibility and stability of data from multiple sources and validate the SCLC consensus nomenclature on the basis of expression of master transcription factors NEUROD1, ASCL1, POU2F3, and YAP1. Our analyses reveal transcription networks linking SCLC subtypes with MYC and its paralogs and the NOTCH and HIPPO pathways. SCLC subsets express specific surface markers, providing potential opportunities for antibody-based targeted therapies. YAP1-driven SCLCs are notable for differential expression of the NOTCH pathway, epithelial-mesenchymal transition (EMT), and antigen-presenting machinery (APM) genes and sensitivity to mTOR and AKT inhibitors. These analyses provide insights into SCLC biology and a framework for future investigations into subtype-specific SCLC vulnerabilities., In Brief Tlemsani et al. provide a unique resource, SCLC-CellMiner, integrating drug sensitivity and multi-omics data from 118 small cell lung cancer (SCLC) cell lines. They demonstrate that SCLCs have differential transcriptional networks driven by lineage-specific transcription factors (NEUROD1, ASCL1, POU2F3, and YAP1). Furthermore, YAP1-driven SCLCs have distinct drug sensitivity profiles., Graphical Abstract
- Published
- 2020