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

被引:111
作者
Tlemsani, Camille [1 ,6 ]
Pongor, Lorinc [1 ]
Elloumi, Fathi [1 ]
Girard, Luc [4 ]
Huffman, Kenneth E. [4 ]
Roper, Nitin [1 ]
Varma, Sudhir [1 ]
Luna, Augustin [5 ]
Rajapakse, Vinodh N. [1 ]
Sebastian, Robin [1 ]
Kohn, Kurt W. [1 ]
Krushkal, Julia [2 ]
Aladjem, Mirit, I [1 ]
Teicher, Beverly A. [2 ]
Meltzer, Paul S. [3 ]
Reinhold, William C. [1 ]
Minna, John D. [4 ]
Thomas, Anish [1 ]
Pommier, Yves [1 ]
机构
[1] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[2] NCI, Biometr Res Program, Div Canc Treatment & Diag, NIH, 9609 Med Ctr Dr, Rockville, MD 20850 USA
[3] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA
[4] UT Southwestern Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA
[5] Dana Farber Canc Inst, cBio Ctr, Dept Data Sci, Div Biostat, Boston, MA 02115 USA
[6] Paris Descartes Univ, Cochin Inst, INSERM U1016, F-75014 Paris, France
来源
CELL REPORTS | 2020年 / 33卷 / 03期
关键词
DNA METHYLATION; MYC; EXPRESSION; GENE; AMPLIFICATION; PACKAGE; INTEGRATION; TRANSCRIPT; LANDSCAPE; EVOLUTION;
D O I
10.1016/j.celrep.2020.108296
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
CellMiner-SCLC (https://discover.nci.nih.gov/ScicCellMinerCDB/) 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, ASCU , 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.
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收藏
页数:20
相关论文
共 69 条
[51]   CellMiner: A Web-Based Suite of Genomic and Pharmacologic Tools to Explore Transcript and Drug Patterns in the NCI-60 Cell Line Set [J].
Reinhold, William C. ;
Sunshine, Margot ;
Liu, Hongfang ;
Varma, Sudhir ;
Kohn, Kurt W. ;
Morris, Joel ;
Doroshow, James ;
Pommier, Yves .
CANCER RESEARCH, 2012, 72 (14) :3499-3511
[52]   ONECUT2 is a targetable master regulator of lethal prostate cancer that suppresses the androgen axis [J].
Rotinen, Mirja ;
You, Sungyong ;
Yang, Julie ;
Coetzee, Simon G. ;
Reis-Sobreiro, Mariana ;
Huang, Wen-Chin ;
Huang, Fangjin ;
Pan, Xinlei ;
Yanez, Alberto ;
Hazelett, Dennis J. ;
Chu, Chia-Yi ;
Steadman, Kenneth ;
Morrissey, Colm M. ;
Nelson, Peter S. ;
Corey, Eva ;
Chung, Leland W. K. ;
Freedland, Stephen J. ;
Di Vizio, Dolores ;
Garraway, Isla P. ;
Murali, Ramachandran ;
Knudsen, Beatrice S. ;
Freeman, Michael R. .
NATURE MEDICINE, 2018, 24 (12) :1887-+
[53]  
Rudin C.M., 2017, SCRX16 001 INVESTIGA
[54]   Phase II Study of Single-Agent Navitoclax (ABT-263) and Biomarker Correlates in Patients with Relapsed Small Cell Lung Cancer [J].
Rudin, Charles M. ;
Hann, Christine L. ;
Garon, Edward B. ;
de Oliveira, Moacyr Ribeiro ;
Bonomi, Philip D. ;
Camidge, D. Ross ;
Chu, Quincy ;
Giaccone, Giuseppe ;
Khaira, Divis ;
Ramalingam, Suresh S. ;
Ranson, Malcolm R. ;
Dive, Caroline ;
McKeegan, Evelyn M. ;
Chyla, Brenda J. ;
Dowell, Barry L. ;
Chakravartty, Arunava ;
Nolan, Cathy E. ;
Rudersdorf, Niki ;
Busman, Todd A. ;
Mabry, Mack H. ;
Krivoshik, Andrew P. ;
Humerickhouse, Rod A. ;
Shapiro, Geoffrey I. ;
Gandhi, Leena .
CLINICAL CANCER RESEARCH, 2012, 18 (11) :3163-3169
[55]   Small cell lung cancer: Time to revisit DNA-damaging chemotherapy [J].
Thomas, Anish ;
Pommier, Yves .
SCIENCE TRANSLATIONAL MEDICINE, 2016, 8 (346)
[56]   ChAMP: updated methylation analysis pipeline for Illumina BeadChips [J].
Tian, Yuan ;
Morris, Tiffany J. ;
Webster, Amy P. ;
Yang, Zhen ;
Beck, Stephan ;
Feber, Andrew ;
Teschendorff, Andrew E. .
BIOINFORMATICS, 2017, 33 (24) :3982-3984
[57]   YAP/TAZ upstream signals and downstream responses [J].
Totaro, Antonio ;
Panciera, Tito ;
Piccolo, Stefano .
NATURE CELL BIOLOGY, 2018, 20 (08) :888-899
[58]   Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks [J].
Trapnell, Cole ;
Roberts, Adam ;
Goff, Loyal ;
Pertea, Geo ;
Kim, Daehwan ;
Kelley, David R. ;
Pimentel, Harold ;
Salzberg, Steven L. ;
Rinn, John L. ;
Pachter, Lior .
NATURE PROTOCOLS, 2012, 7 (03) :562-578
[59]  
van der Maaten L, 2014, J MACH LEARN RES, V15, P3221
[60]  
Wang Huixia, 2006, BMC Genomics, V7, P166