SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures
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 ca...
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doaj-c3a89008a1ef48f497155a5b22995bc32020-11-25T03:45:07ZengElsevierCell Reports2211-12472020-10-01333108296SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic SignaturesCamille Tlemsani0Lorinc Pongor1Fathi Elloumi2Luc Girard3Kenneth E. Huffman4Nitin Roper5Sudhir Varma6Augustin Luna7Vinodh N. Rajapakse8Robin Sebastian9Kurt W. Kohn10Julia Krushkal11Mirit I. Aladjem12Beverly A. Teicher13Paul S. Meltzer14William C. Reinhold15John D. Minna16Anish Thomas17Yves Pommier18Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USADevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USADevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USAHamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75390, USAHamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75390, USADevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USADevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USAcBio Center, Division of Biostatistics, Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA 02115, USADevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USADevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USADevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USABiometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, 9609 Medical Center Drive, Rockville, MD 20850, USADevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USABiometric Research Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, 9609 Medical Center Drive, Rockville, MD 20850, USAGenetics Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USADevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USAHamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75390, USADevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USADevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124720312857SchlafenSLFN11STINGnative immune responsegenomicsimmune checkpoints |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures Cell Reports Schlafen SLFN11 STING native immune response genomics immune checkpoints |
author_facet |
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 |
author_sort |
Camille Tlemsani |
title |
SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures |
title_short |
SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures |
title_full |
SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures |
title_fullStr |
SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures |
title_full_unstemmed |
SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures |
title_sort |
sclc-cellminer: a resource for small cell lung cancer cell line genomics and pharmacology based on genomic signatures |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2020-10-01 |
description |
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. |
topic |
Schlafen SLFN11 STING native immune response genomics immune checkpoints |
url |
http://www.sciencedirect.com/science/article/pii/S2211124720312857 |
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