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Next-generation characterization of the Cancer Cell Line Encyclopedia
Open accessAbstract
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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“Through systematic mining of databases for correlations between the cytotoxicity of 4,518 clinical and pre-clinical small molecules and E3 ligase expression levels across hundreds of human cancer cell lines,3–5 we identified CR8, a cyclin-dependent kinase (CDK) inhibitor,6 as a compound that acts as a molecular glue degrader.”
From The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K (2020) · cites this paper as [5]
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Synthetic lethality of mRNA quality control complexes in cancer
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“The CRISPR revolution and genomic profiling technologies, spearheaded by large consortium efforts such as the Cancer Dependency Map (DepMap) 8 and Cancer Cell Line Encyclopedia 9,10 have enabled several novel discoveries over the past decade.”
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A pan-cancer survey of cell line tumor similarity by feature-weighted molecular profiles
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Modeling drug combination effects via latent tensor reconstruction
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Sanchez‐Burgos, L., Navarro‐González, B., García‐Martín, S., Sirozh, O., Mota‐Pino, J., Fueyo‐Marcos, E., Tejero, H., Antón, M. E., Murga, M., Al‐Shahrour, F., et al. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202215855 · Cited by 27
“This profound MDR phenotype of FBXW7 mutant cells was also observed by interrogating the Cancer Cell Line Encyclopedia (CCLE), which contains data from 1,072 cell lines (Ghandi et al, 2019; Fig 1E).”
BackgroundPulmonary neuroendocrine cells sense succinate to stimulate myoepithelial cell contraction
Yu, W., Moninger, T. O., Rector, M. V., Stoltz, D. A., & Welsh, M. J. (2022) · Developmental Cell · doi:10.1016/j.devcel.2022.08.010 · Cited by 27
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“Meanwhile, the cell line features such as gene mutation and genomic data are obtained from CCLE and the Cancer Dependency Map (CDM).”
MethodMolecular markers of metastatic disease in KRAS-mutant lung adenocarcinoma
Boiarsky, D., Lydon, C., Chambers, E. S., Sholl, L. M., Nishino, M., Skoulidis, F., Heymach, J. V., Luo, J., Awad, M. M., Janne, P. A., et al. (2023) · Annals of Oncology · doi:10.1016/j.annonc.2023.04.514 · Cited by 32
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“Similarly, we noted a significant enrichment of the angiogenic/ stromal and angiogenic clusters within the regulon-activated phenotype (125 [74”
BackgroundPrevalence and Therapeutic Targeting of High-Level ERBB2 Amplification in NSCLC
Odintsov, I., Makarem, M., Nishino, M., Bachert, S. E., Zhang, T., LoPiccolo, J., Paweletz, C. P., Gokhale, P. C., Ivanova, E. V., Saldanha, A. L., et al. (2023) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2023.12.019 · Cited by 27
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“Cell line information was cross-referenced with Cellosaurus [ 42 ] and CCLE [ 41 ] to incorporate additional annotations, including synonyms and disease indications.”
GEDS: A Gene Expression Display Server for mRNAs, miRNAs and Proteins
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Self-citationBest Practices for Technical Reproducibility Assessment of Multiplex Immunofluorescence
Laberiano-Fernández, C., Ruiz, S. H., Rojas, F. R., & Parra, E. R. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.660202 · Cited by 27
FGF signalling facilitates cervical cancer progression
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Novel Diagnostic and Therapeutic Options for KMT2A-Rearranged Acute Leukemias
Lopes, B. A., Poubel, C. P., Teixeira, C. E., Caye‐Eude, A., Cavé, H., Meyer, C., Marschalek, R., Boroni, M., & Emerenciano, M. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.749472 · Cited by 27
“RNA-seq profiling was performed as previously described (Ghandi et al., 2019), and reads were aligned to the GRCh37 human genome reference.”
Method3D genome organization in the epithelial-mesenchymal transition spectrum
Pang, Q. Y., Tan, T. Z., Sundararajan, V., Chiu, Y.-C., Chee, E. Y. W., Chung, V. Y., Choolani, M. A., & Huang, R. Y. (2022) · Genome biology · doi:10.1186/s13059-022-02687-x · Cited by 27
“RNA‐seq data for the cell lines MCF7, PANC1, A549, and HEYA8 were downloaded from Cancer Dependency Portal (Dep‐ Map) under “DepMap Public 20Q2” release [109].”
MethodAmplified EPOR / JAK2 Genes Define a Unique Subtype of Acute Erythroid Leukemia
Takeda, J., Yoshida, K., Nakagawa, M. M., Nannya, Y., Yoda, A., Saiki, R., Ochi, Y., Zhao, L., Okuda, R., Qi, X., et al. (2022) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-21-0192 · Cited by 28
“We chose these cell lines because K562 is known to have high expression of JAK2 (37), and OCI-M2 has a focal amplification and overexpression of EPOR (ref.”
MethodA Pan-Cancer Analysis Reveals CLEC5A as a Biomarker for Cancer Immunity and Prognosis
Chen, R., Wu, W., Chen, S., Liu, Z.-Z., Wen, Z., Yu, J., Zhang, L.-B., Liu, Z., Zhang, J., Luo, P., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.831542 · Cited by 26
CHAMP1 binds to REV7/FANCV and promotes homologous recombination repair
Li, F., Sarangi, P., Iyer, D., Feng, H., Moreau, L. A., Nguyen, H. Q., Clairmont, C. S., & D’Andrea, A. D. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111297 · Cited by 28
“…and CHAMP1 expression in cancer cell lines were performed using the RNASeq expression data from the Cancer Cell Line Encyclopedia (CCLE) project (Ghandi et al., 2019) and the dependency data from the Broad Institute Cancer Dependency Map (DepMap; CRISPR DepMap Public 19Q4 dataset) (Meyers et…”
Opportunities for pharmacoproteomics in biomarker discovery
Poulos, R. C., Cai, Z., Robinson, P. J., Reddel, R. R., & Zhong, Q. (2022) · PROTEOMICS · doi:10.1002/pmic.202200031 · Cited by 27
Sullivan, D. K., Deutzmann, A., Yarbrough, J., Krishnan, M. S., Gouw, A. M., Bellovin, D. I., Adam, S. J., Liefwalker, D. F., Dhanasekaran, R., & Felsher, D. W. (2022) · Oncogene · doi:10.1038/s41388-022-02458-9 · Cited by 26
“RNA-seq TPM data from the Cancer Cell Line Encyclopedia (CCLE) was obtained from the Broad Institute and this data was further normalized using the DESeq2 method followed by log2-transformation.”
MethodInfluentialde Carvalho, F. V., Ribeiro, L. N. D. M., de Moura, L. D., da Silva, G. H. R., Mitsutake, H., Mendonça, T. C., Gerônimo, G., Breitkreitz, M. C., & de Paula, E. (2022) · Molecules · doi:10.3390/molecules27248838 · Cited by 27
“Cancer is the name given to a set of diseases that cause disordered cell growth; the neoplastic cells being able to survive and spread to other tissues and organs [1].”
BackgroundNeyret‐Kahn, H., Fontugne, J., Meng, X. Y., Groeneveld, C. S., Cabel, L., Ye, T., Guyon, E., Krucker, C., Dufour, F., Chapeaublanc, E., et al. (2023) · Oncogene · doi:10.1038/s41388-023-02662-1 · Cited by 27
“The reference tumours for RNA-seq cell line samples were TCGA-BLCA RNA-seq tumour transcriptomes (n= 430) and normalized in accordance with the cell line normalization, namely TPM for CCLE samples and RLE for MDA samples.”
InfluentialGoulding, J., Yeh, W.-I., Hancock, B., Blum, R., Xu, T., Yang, B.-H., Chang, C., Groff, B. C., Avramis, E. V., Pribadi, M., et al. (2023) · Med · doi:10.1016/j.medj.2023.04.004 · Cited by 28
Niacin restriction with NAMPT-inhibition is synthetic lethal to neuroendocrine carcinoma
Nomura, M., Ohuchi, M., Sakamoto, Y., Kudo, K., Yaku, K., Soga, T., Sugiura, Y., Morita, M., Hayashi, K., Miyahara, S., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-43630-3 · Cited by 29
Size-scaling promotes senescence-like changes in proteome and organelle contentPreprint
Cheng, L., Chen, J., Kong, Y., Tan, C., Kafri, R., & Björklund, M. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.05.455193 · Cited by 28
Fujita, M., Chen, M.-J. M., Siwak, D. R., Sasagawa, S., Oosawa-Tatsuguchi, A., Arihiro, K., Ono, A., Miura, R., Maejima, K., Aikata, H., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34249-x · Cited by 24
Self-citationC16orf72/HAPSTR1 is a molecular rheostat in an integrated network of stress response pathways
Amici, D. R., Ansel, D. J., Metz, K. A., Smith, R. S., Phoumyvong, C. M., Gayatri, S., Chamera, T., Edwards, S. L., O’Hara, B. P., Srivastava, S., et al. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2111262119 · Cited by 29
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“Given that specific mutations in a protein may affect its biological function, we searched the Cancer Cell Line Encyclopedia (28) and collected 6 natural missense mutations of DDX3X in cancer (Supplemental Figure 1G).”
Guo, S., Liu, Y., Sun, Y., Zhou, H., Gao, Y., Wang, P., Zhi, H., Zhang, Y., Gan, J., & Ning, S. (2024) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c01473 · Cited by 33
Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer
Hosseini, A., Lindholm, H. T., Chen, R. E., Mehdipour, P., Marhon, S. A., Ishak, C. A., Moore, P. C., Classon, M., Gioacchino, A. D., Greenbaum, B. D., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.113684 · Cited by 30
“…editing levels in these cell lines were estimated by a modified pipeline based on variant calling in RNA sequencing (RNA-seq) data from the CCLE 19 and revealed active A-to-I editing with 19,255 and 20,023 A-to-I editing loci in the XRN1-resistant cell lines NCI-H716 and COLO678, respectively,…”
InfluentialCD8 + T cell targeting of tumor antigens presented by HLA-E
Iyer, R. F., Verweij, M. C., Nair, S. S., Morrow, D., Mansouri, M., Chakravarty, D., Beechwood, T., Meyer, C., Uebelhoer, L. S., Lauron, E. J., et al. (2024) · Science Advances · doi:10.1126/sciadv.adm7515 · Cited by 26
“We selected the four cell lines 22RV1, LNCaP, VCaP, and DU145 representing a range of HLA-I, HLA-E, and PAP expression based on published mRNA expression profiles ( 72 ).”
RPL22 is a tumor suppressor in MSI-high cancers and a splicing regulator of MDM4
Weinstein, H. N. W., Hu, K., Fish, L., Chen, Y.-A., Allegakoen, P., Pham, J. H., Hui, K. S. F., Chang, C., Tutar, M., Benitez-Rivera, L., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114622 · Cited by 28
Self-citationJiménez‐Santos, M. J., García‐Martín, S., Rubio‐Fernández, M., Goméz-López, G., & Al‐Shahrour, F. (2024) · NAR Cancer · doi:10.1093/narcan/zcae046 · Cited by 33
Tedeschi, A., Schischlik, F., Rocchetti, F., Popow, J., Ebner, F., Gerlach, D., Geyer, A., Santoro, V., Boghossian, A. S., Rees, M. G., et al. (2024) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-24-0386 · Cited by 28
UQCRH downregulation promotes Warburg effect in renal cell carcinoma cells
Luo, Y., Bengtsson, L. M., Wang, X., Huang, T., Liu, G., Murphy, S. P., Wang, C., Koren, J., Schafer, Z. T., & Lü, X. (2020) · Scientific Reports · doi:10.1038/s41598-020-72107-2 · Cited by 27
CEN‐tools: an integrative platform to identify the contexts of essential genes
Sharma, S., Dinçer, C., Weidemüller, P., Wright, G. J., & Petsalaki, E. (2020) · Molecular Systems Biology · doi:10.15252/msb.20209698 · Cited by 25
Pratt, D. W., Kumar‐Sinha, C., Cieslik, M. P., Mehra, R., Xiao, H., Shao, L., Franson, A. T., Cantor, E., Chinnaiyan, A. M., Mody, R. J., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02278-3 · Cited by 26
Cheng, S., Yang, S., Shi, Y., Shi, R., Yeh, Y. A., & Yu, X. (2021) · Scientific Reports · doi:10.1038/s41598-021-82472-1 · Cited by 26
Detection of Molecular Signatures of Homologous Recombination Deficiency in Bladder Cancer
Börcsök, J., Dióssy, M., Sztupinszki, Z. M., Prósz, A. G., Tisza, V., Spisák, S., Rusz, O., Stormoen, D. R., Pappot, H., Csabai, I., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-5037 · Cited by 27
Örd, T., Örd, D., Kaikkonen, M. U., & Örd, T. (2021) · Cancers · doi:10.3390/cancers13102341 · Cited by 26
Wang, L., Wang, Y., Wang, J., Li, L., & Bi, J. (2021) · Journal of Immunology Research · doi:10.1155/2021/3236384 · Cited by 28
Wang, D., Peng, L., Hua, L., Li, J., Liu, Y., & Zhou, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.817800 · Cited by 26
“were obtained from the Cancer Cell Line Encyclopedia (CCLE) dataset(2) (Ghandi et al., 2019).”
MethodErtl, I. E., Lemberger, U. J., Ilijazi, D., Hassler, M. R., Bruchbacher, A., Brettner, R., Kronabitter, H., Gutmann, M., Vician, P., Zeitler, G., et al. (2022) · European Urology · doi:10.1016/j.eururo.2022.03.009 · Cited by 26
Systematic characterization of cancer transcriptome at transcript resolution
Hu, W., Wu, Y., Shi, Q., Wu, J., Kong, D., Wu, X., He, X., Liu, T., & Li, S. (2022) · Nature Communications · doi:10.1038/s41467-022-34568-z · Cited by 25
Clinical proteomics towards multiomics in cancer
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Applications of Genome-Wide Screening and Systems Biology Approaches in Drug Repositioning
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Preclinical Models for the Study of Lung Cancer Pathogenesis and Therapy DevelopmentPreprint
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Prediction model for drug response of acute myeloid leukemia patients
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“Data from the CCLE database were already preprocessed according to standard pipelines 87,88 and then scaled using the R scale method.”
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Transcript-specific enrichment enables profiling of rare cell states via single-cell RNA sequencing
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Molecular subtypes of intrahepatic cholangiocarcinoma
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Analysis of CRISPR‐Cas9 screens identifies genetic dependencies in melanoma
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PAX9 Determines Epigenetic State Transition and Cell Fate in Cancer
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“The lncRNA transcript expression pro fi les in different normal human tissues and multiple types of cancer cell lines were retrieved from LncExpDB (Li et al., 2021) and were previously collected from the Human Protein Atlas (HPA) (Uhlen et al., 2017) and the Cancer Cell Line Encyclopedia (CCLE) (Ghandi et al., 2019), r…”
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Integrated screens uncover a cell surface tumor suppressor gene KIRREL involved in Hippo pathway
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“In addition, from the CCLE 2019 release [24] (https://depmap.”
Background
Metadata
- 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
- Published
- 2019-05
- Volume
- 569
- Issue
- 7757
- Pages
- 503-508
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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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