SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures

• Published in: Cell reports (Cambridge) Vol. 33; no. 3; p. 108296
• Main Authors: Tlemsani, Camille, Pongor, Lorinc, Elloumi, Fathi, Girard, Luc, Huffman, Kenneth E., Roper, Nitin, Varma, Sudhir, Luna, Augustin, Rajapakse, Vinodh N., Sebastian, Robin, Kohn, Kurt W., Krushkal, Julia, Aladjem, Mirit I., Teicher, Beverly A., Meltzer, Paul S., Reinhold, William C., Minna, John D., Thomas, Anish, Pommier, Yves
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.10.2020; Elsevier
• Subjects: Algorithms; Cell Line, Tumor; Data Mining - methods; DNA Methylation - genetics; Epigenesis, Genetic - genetics; Epigenomics - methods; Epithelial-Mesenchymal Transition - genetics; Gene Expression Regulation, Neoplastic - genetics; genomics; Genomics - methods; Humans; immune checkpoints; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; mutations; native immune response; neuroendocrine tumors; PARP; Pharmacological and Toxicological Phenomena; replication; Reproducibility of Results; Schlafen; SLFN11; Small Cell Lung Carcinoma - genetics; Small Cell Lung Carcinoma - metabolism; Software; STING; Transcription Factors - genetics; Schlafen; replication; SLFN11; mutations; STING; native immune response; genomics; PARP; neuroendocrine tumors; immune checkpoints
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108296

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. [Display omitted] •SCLC-CellMiner is an extensive cell line genomic and pharmacology resource•SCLC cell lines show a methylome consistent with their plasticity and lineage•Transcriptome analyses reveal lineage transcriptional networks and drug predictions•SCLC-Y cells differ from other subgroups by transcriptome and potential therapeutics 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.