Cited by 3,394Cancer Genomics and DiagnosticsChromatin Remodeling and CancerGene expression and cancer classification

The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.

Next-generation characterization of the Cancer Cell Line Encyclopedia

Open access

Ghandi, Mahmoud, Huang, Franklin W., Jané-Valbuena, Judit, Kryukov, Gregory V., Lo, Christopher C., McDonald, E. Robert, Barretina, Jordi, Gelfand, Ellen T., Bielski, Craig M., Li, Haoxin, Hu, Kevin, Andreev-Drakhlin, Alexander Y., Kim, Jaegil, Hess, Julian M., Haas, Brian J., Aguet, François, Weir, Barbara A., Rothberg, Michael V., Paolella, Brenton R., Lawrence, Michael S., Akbani, Rehan, Lu, Yiling, Tiv, Hong L., Gokhale, Prafulla C., de Weck, Antoine, Mansour, Ali Amin, Oh, Coyin, Shih, Juliann, Hadi, Kevin, Rosen, Yanay, Bistline, Jonathan, Venkatesan, Kavitha, Reddy, Anupama, Sonkin, Dmitriy, Liu, Manway, Lehar, Joseph, Korn, Joshua M., Porter, Dale A., Jones, Michael D., Golji, Javad, Caponigro, Giordano, Taylor, Jordan E., Dunning, Caitlin M., Creech, Amanda L., Warren, Allison C., McFarland, James M., Zamanighomi, Mahdi, Kauffmann, Audrey, Stransky, Nicolas, Imielinski, Marcin, Maruvka, Yosef E., Cherniack, Andrew D., Tsherniak, Aviad, Vazquez, Francisca, Jaffe, Jacob D., Lane, Andrew A., Weinstock, David M., Johannessen, Cory M., Morrissey, Michael P., Stegmeier, Frank, Schlegel, Robert, Hahn, William C., Getz, Gad, Mills, Gordon B., Boehm, Jesse S., Golub, Todd R., Garraway, Levi A., Sellers, William R.·2019·Nature

DOI 10.1038/s41586-019-1186-3PMC PMC6697103

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Abstract

Large panels of comprehensively characterized human cancer models, including the Cancer Cell Line Encyclopedia (CCLE), have provided a rigorous framework with which to study genetic variants, candidate targets, and small-molecule and biological therapeutics and to identify new marker-driven cancer dependencies. To improve our understanding of the molecular features that contribute to cancer phenotypes, including drug responses, here we have expanded the characterizations of cancer cell lines to include genetic, RNA splicing, DNA methylation, histone H3 modification, microRNA expression and reverse-phase protein array data for 1,072 cell lines from individuals of various lineages and ethnicities. Integration of these data with functional characterizations such as drug-sensitivity, short hairpin RNA knockdown and CRISPR–Cas9 knockout data reveals potential targets for cancer drugs and associated biomarkers. Together, this dataset and an accompanying public data portal provide a resource for the acceleration of cancer research using model cancer cell lines. The original Cancer Cell Line Encyclopedia (CCLE) is expanded with deeper characterization of over 1,000 cell lines, including genomic, transcriptomic, and proteomic data, and integration with drug-sensitivity and gene-dependency data.

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A comprehensive evaluation of computational tools to identify differential methylation regions using RRBS data
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Designing custom CRISPR libraries for hypothesis-driven drug target discovery
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Identification of key genes and functions of circulating tumor cells in multiple cancers through bioinformatic analysis
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Identification of tumor mutation burden-related hub genes and the underlying mechanism in melanoma
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The landscape of metabolic pathway dependencies in cancer cell lines
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KIF18B is a Prognostic Biomarker and Correlates with Immune Infiltrates in Pan-Cancer
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Combination of resveratrol and BIBR1532 inhibits proliferation of colon cancer cells by repressing expression of LncRNAs
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Method
Identifying essential genes across eukaryotes by machine learning
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Predictive and Therapeutic Implications of a Novel PLCγ1/SHP2-Driven Mechanism of Cetuximab Resistance in Metastatic Colorectal Cancer
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CDK3, CDK5 and CDK8 Proteins as Prognostic and Potential Biomarkers in Colorectal Cancer Patients
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Silver Clusters of Five Atoms as Highly Selective Antitumoral Agents Through Irreversible Oxidation of Thiols
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“To evaluate the association of serglycin expression with EMT in breast cancer, we started by examining RNA-Seq data from 48 breast cancer cell lines deposited to the Cancer Cell Line Encyclopedia (40).”
Method
Deciphering the tumor microenvironment cell–infiltrating landscape reveals microenvironment subtypes and therapeutic potentials for nonsquamous NSCLC
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Comprehensive Analysis of Prognostic Value and Immune Infiltration of NLRC4 and CASP1 in Colorectal Cancer
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“Using this database, we analyzed the differential mRNA expression of NLRC4 and CASP1 in CRC tissues and normal tissues, and further explored the association between NLRC4 and CASP1 and revealed their diagnostic value in CRC. Cancer Cell Line Encyclopedia (CCLE, www.broadinstitute.org/ccle) collected the public informa…”
Method
Cell and Animal Models for SARS-CoV-2 Research
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DSMZCellDive: Diving into high-throughput cell line data
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Comparative kinase and cancer cell panel profiling of kinase inhibitors approved for clinical use from 2018 to 2020
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Method
Targeting breast and pancreatic cancer metastasis using a dual-cadherin antibody
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Reduced IQGAP2 Promotes Bladder Cancer through Regulation of MAPK/ERK Pathway and Cytokines
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“Cancer Cell Line Encyclopedia (CCLE) (https://portals.broadinstitute.org/ccle) includes the large-scale in-depth sequencing of 947 human cancer cell lines, covering more than 30 tissue sources and integrating genetic information, such as DNA mutations, gene expressions, and chromosome copy numbers [22].”
BackgroundMethodInfluential
Expression dynamics of periodic transcripts during cancer cell cycle progression and their correlation with anticancer drug sensitivity
Li, C., Wang, J., Wang, W., Xu, D., Zhou, Y., Sun, F., Li, Y., Guo, F., Ma, J.-L., Zhang, X., et al. (2022) · Military Medical Research · doi:10.1186/s40779-022-00432-w · Cited by 22
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Method
Patient-derived cell-based pharmacogenomic assessment to unveil underlying resistance mechanisms and novel therapeutics for advanced lung cancer
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“To compare alpelisib response of RB1/TP53 cells between PDCs and cell lines, we additionally collected drug screening dataset of CCLE lung cancer cell lines (n = 70) to include SCLC (n = 7) [5].”
MethodSelf-citation
Simultaneous activation of CXC chemokine receptor 4 and histamine receptor H1 enhances calcium signaling and cancer cell migration
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Oxidative stress enhances the therapeutic action of a respiratory inhibitor in MYC‐driven lymphoma
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“All of the Pgd KO FLMycER clones obtained were heterozygous, with residual Pgd protein expression (Appendix Fig S3I), consistent with the essential nature of this gene, as defined in the Broad Institute Dependency Map (DepMap) portal (Ghandi et al, 2019).”
TAZ2 truncation confers overactivation of p300 and cellular vulnerability to HDAC inhibition
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LILRB3 Modulates Acute Myeloid Leukemia Progression and Acts as an Effective Target for CAR T-cell Therapy
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Self-citation
INPP5A phosphatase is a synthetic lethal target in GNAQ and GNA11-mutant melanomas
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Exercise potentially prevents colorectal cancer liver metastases by suppressing tumor epithelial cell stemness via RPS4X downregulation
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“0.3) [44].”
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Synthetic Lethal Targeting of Mitotic Checkpoints in HPV-Negative Head and Neck Cancer
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Evaluation of an aldo-keto reductase gene signature with prognostic significance in colon cancer via activation of epithelial to mesenchymal transition and the p70S6K pathway
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Multiomics analysis reveals CT83 is the most specific gene for triple negative breast cancer and its hypomethylation is oncogenic in breast cancer
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Radiopotentiation Profiling of Multiple Inhibitors of the DNA Damage Response for Early Clinical Development
Gill, S. J., Wijnhoven, P. W. G., Fok, J. H. L., Lloyd, R. L., Cairns, J., Armenia, J., Nikkilä, J., Lau, A., Bakkenist, C. J., Galbraith, S. M., et al. (2021) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-20-0502 · Cited by 23
Cotargeting a MYC/eIF4A-survival axis improves the efficacy of KRAS inhibitors in lung cancer
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“MYC allelic copy number was characterized as deletion, diploid, or amplification (39).”
Self-citation
A proteomic platform to identify off-target proteins associated with therapeutic modalities that induce protein degradation or gene silencing
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Background
Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition
Shendy, N. A. M., Bikowitz, M. J., Sigua, L. H., Zhang, Y., Mercier, A. L., Khashana, Y., Nance, S., Liu, Q., Delahunty, I. M., Robinson, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-47102-0 · Cited by 21
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Leveraging Patient-Derived Organoids for Personalized Liver Cancer Treatment
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Background
RSK1 is an exploitable dependency in myeloproliferative neoplasms and secondary acute myeloid leukemia
Kong, T., Laranjeira, A. B. A., Letson, C. T., Yu, L. C., Lin, S., Fowles, J. S., Fisher, D. A. C., Ng, S., Yang, W., He, F., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55643-7 · Cited by 22
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The Reprimo-Like Gene Is an Epigenetic-Mediated Tumor Suppressor and a Candidate Biomarker for the Non-Invasive Detection of Gastric Cancer
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A bioinformatic analysis of the inhibin-betaglycan-endoglin/CD105 network reveals prognostic value in multiple solid tumors
Listik, E., Horst, B., Choi, A. S., Lee, N. Y., Győrffy, B., & Mythreye, K. (2021) · PLoS ONE · doi:10.1371/journal.pone.0249558 · Cited by 21
Expression and prognostic potential of PLEK2 in head and neck squamous cell carcinoma based on bioinformatics analysis
Wang, J., Sun, Z., Wang, J., Tian, Q., Huang, R., Wang, H., Wang, X., & Han, F. (2021) · Cancer Medicine · doi:10.1002/cam4.4163 · Cited by 21

Authors: Ghandi, M., Huang, F. W., Jané-Valbuena, J., Kryukov, G. V., Lo, C. C., McDonald, E. R., Barretina, J., Gelfand, E. T., Bielski, C. M., Li, H., Hu, K., Andreev-Drakhlin, A. Y., Kim, J., Hess, J. M., Haas, B. J., Aguet, F., Weir, B. A., Rothberg, M. V., Paolella, B. R., Lawrence, M. S., Akbani, R., Lu, Y., Tiv, H. L., Gokhale, P. C., de Weck, A., Mansour, A. A., Oh, C., Shih, J., Hadi, K., Rosen, Y., Bistline, J., Venkatesan, K., Reddy, A., Sonkin, D., Liu, M., Lehar, J., Korn, J. M., Porter, D. A., Jones, M. D., Golji, J., Caponigro, G., Taylor, J. E., Dunning, C. M., Creech, A. L., Warren, A. C., McFarland, J. M., Zamanighomi, M., Kauffmann, A., Stransky, N., Imielinski, M., Maruvka, Y. E., Cherniack, A. D., Tsherniak, A., Vazquez, F., Jaffe, J. D., Lane, A. A., Weinstock, D. M., Johannessen, C. M., Morrissey, M. P., Stegmeier, F., Schlegel, R., Hahn, W. C., Getz, G., Mills, G. B., Boehm, J. S., Golub, T. R., Garraway, L. A., & Sellers, W. R.
Affiliations: Broad Institute (US)
The University of Texas MD Anderson Cancer Center (US)
Cornell University (US)
National Cancer Institute (US)
Novartis Institutes for BioMedical Research (CH)
Dana-Farber Cancer Institute (US)
Corresponding author: Sellers, William R.
ORCID: Ghandi, Mahmoud
Huang, Franklin W.
Kryukov, Gregory V.
McDonald, E. Robert
Barretina, Jordi
Li, Haoxin
Hu, Kevin
Andreev-Drakhlin, Alexander Y.
Kim, Jaegil
Hess, Julian M.
Haas, Brian J.
Aguet, François
Rothberg, Michael V.
Paolella, Brenton R.
Lawrence, Michael S.
Akbani, Rehan
Lu, Yiling
Tiv, Hong L.
Gokhale, Prafulla C.
Oh, Coyin
Shih, Juliann
Hadi, Kevin
Rosen, Yanay
Venkatesan, Kavitha
Reddy, Anupama
Sonkin, Dmitriy
Liu, Manway
Korn, Joshua M.
Jones, Michael D.
Taylor, Jordan E.
Creech, Amanda L.
McFarland, James M.
Zamanighomi, Mahdi
Kauffmann, Audrey
Stransky, Nicolas
Imielinski, Marcin
Maruvka, Yosef E.
Cherniack, Andrew D.
Tsherniak, Aviad
Jaffe, Jacob D.
Lane, Andrew A.
Weinstock, David M.
Johannessen, Cory M.
Stegmeier, Frank
Hahn, William C.
Getz, Gad
Mills, Gordon B.
Boehm, Jesse S.
Golub, Todd R.
Garraway, Levi A.
Sellers, William R.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2019-05
Volume: 569
Issue: 7757
Pages: 503-508
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-019-1186-3
PMC: PMC6697103
OpenAlex: W2944727022
Semantic Scholar: b3631d8d2656c0c72ad92f3b0a77af2afde649a5
Cited by: 3,394
References: 67
Citations by year: 2026: 297 · 2025: 472 · 2024: 560 · 2023: 551 · 2022: 550 · 2021: 594 · 2020: 306 · 2019: 59
FWCI: 121.99
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: European Hematology Association (TRTH56)
National Institutes of Health (5r21da025720-02)
National Institute on Drug Abuse (R21-DA025720)
National Cancer Institute (R50CA221675, P50CA217685, R01CA219943, P50CA098258, U24CA180922, U54CA224068, U24CA210949, U24CA210950, R50CA211461, R37CA225191, U01CA217842, U01CA176058, P30CA016672)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
Keywords: Cancer Cell Line Encyclopedia, cancer cell lines, drug sensitivity, gene dependency, RNA splicing, DNA methylation, histone H3 modifications, microRNA expression, reverse phase protein array, CRISPR/Cas9 knockout, shRNA knockdown, therapeutic target, biomarkers, multi-omics integration, public data portals
MeSH terms: Gene Editing, Antineoplastic Agents, Ethnicity, Histones, Humans, Neoplasms, RNA Splicing, Biomarkers, Tumor, Drug Resistance, Neoplasm, DNA Methylation, MicroRNAs, Protein Array Analysis, Cell Line, Tumor, Molecular Targeted Therapy

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Next-generation characterization of the Cancer Cell Line Encyclopedia

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