SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures
Camille Tlemsani,
Lorinc Pongor,
Fathi Elloumi,
Luc Girard,
Kenneth E. Huffman,
Nitin Roper,
Sudhir Varma,
Augustin Luna,
Vinodh N. Rajapakse,
Robin Sebastian,
Kurt W. Kohn,
Julia Krushkal,
Mirit I. Aladjem,
Beverly A. Teicher,
Paul S. Meltzer,
William C. Reinhold,
John D. Minna,
Anish Thomas,
Yves Pommier
Affiliations
Camille Tlemsani
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Lorinc Pongor
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Fathi Elloumi
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Luc Girard
Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75390, USA
Kenneth E. Huffman
Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75390, USA
Nitin Roper
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Sudhir Varma
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Augustin Luna
cBio Center, Division of Biostatistics, Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA 02115, USA
Vinodh N. Rajapakse
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Robin Sebastian
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Kurt W. Kohn
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Julia Krushkal
Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, 9609 Medical Center Drive, Rockville, MD 20850, USA
Mirit I. Aladjem
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Beverly A. Teicher
Biometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, 9609 Medical Center Drive, Rockville, MD 20850, USA
Paul S. Meltzer
Genetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA
William C. Reinhold
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
John D. Minna
Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75390, USA
Anish Thomas
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA
Yves Pommier
Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Corresponding author
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.
