Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Cell Rep. 2020 Oct 20;33(3):108296. 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.
CellMiner-SCLC(https://discover.nci.nih.gov/SclcCellMinerCDB/)整合了药物敏感性和基因组数据,包括 118 个人源小细胞肺癌(SCLC)细胞系的高分辨率甲基化组和转录组,为研究这种“难治性癌症”提供了资源。我们展示了来自多个来源的数据的可重复性和稳定性,并基于主转录因子 NEUROD1、ASCL1、POU2F3 和 YAP1 的表达验证了 SCLC 共识命名法。我们的分析揭示了将 SCLC 亚型与 MYC 及其同源物以及 NOTCH 和 HIPPO 途径联系起来的转录网络。SCLC 亚组表达特定的表面标志物,为基于抗体的靶向治疗提供了潜在的机会。YAP1 驱动的 SCLC 值得注意的是 NOTCH 途径、上皮-间充质转化(EMT)和抗原呈递机制(APM)基因的差异表达,以及对 mTOR 和 AKT 抑制剂的敏感性。这些分析为 SCLC 生物学提供了深入的了解,并为未来针对 SCLC 亚型特异性脆弱性的研究提供了框架。