Home LiteratureArticle Details
PMID: 23856246 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology.

Cancer research ·Vol. 73 ·No. 14 ·2013-07-15 ·Pages 4372-82

Abaan OD, Polley EC, Davis SR, Zhu YJ, Bilke S, Walker RL, Pineda M, Gindin Y, Jiang Y, Reinhold WC, Holbeck SL, Simon RM, Doroshow JH, Pommier Y, Meltzer PS

Abstract

The NCI-60 cell lines are the most frequently studied human tumor cell lines in cancer research. This panel has generated the most extensive cancer pharmacology database worldwide. In addition, these cell lines have been intensely investigated, providing a unique platform for hypothesis-driven research focused on enhancing our understanding of tumor biology. Here, we report a comprehensive analysis of coding variants in the NCI-60 panel of cell lines identified by whole exome sequencing, providing a list of possible cancer specific variants for the community. Furthermore, we identify pharmacogenomic correlations between specific variants in genes such as TP53, BRAF, ERBBs, and ATAD5 and anticancer agents such as nutlin, vemurafenib, erlotinib, and bleomycin showing one of many ways the data could be used to validate and generate novel hypotheses for further investigation. As new cancer genes are identified through large-scale sequencing studies, the data presented here for the NCI-60 will be an invaluable resource for identifying cell lines with mutations in such genes for hypothesis-driven research. To enhance the utility of the data for the greater research community, the genomic variants are freely available in different formats and from multiple sources including the CellMiner and Ingenuity websites.

MeSH Terms
Antineoplastic Agents Cell Line, Tumor Drug Screening Assays, Antitumor/methods Exome Genetic Variation Humans Mutation Neoplasms/drug therapy,genetics Pharmacogenetics/methods
Chemicals
Antineoplastic Agents
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Abaan Ogan D
Genetics Branch, Laboratory of Molecular Pharmacology, Center for Cancer Research, and Division of Cancer Treatment and Diagnosis, National Cancer Institute, NIH, Bethesda, MD 20982, USA.
Polley Eric C
Davis Sean R
Zhu Yuelin J
Bilke Sven
Walker Robert L
Pineda Marbin
Gindin Yevgeniy
Jiang Yuan
Reinhold William C
Holbeck Susan L
Simon Richard M
Doroshow James H
Pommier Yves
Meltzer Paul S
References (50)
50 references, click to expand
  1. DNA fingerprinting of the NCI-60 cell line panel.
    Mol Cancer Ther. 2009 Apr;8(4):713-24 PMID: 19372543
  2. A map of human genome variation from population-scale sequencing.
    Nature. 2010 Oct 28;467(7319):1061-73 PMID: 20981092
  3. The mechanisms of UV mutagenesis.
    J Radiat Res. 2011;52(2):115-25 PMID: 21436607
  4. COSMIC 2005.
    Br J Cancer. 2006 Jan 30;94(2):318-22 PMID: 16421597
  5. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors.
    Nat Med. 2004 Dec;10(12):1321-8 PMID: 15558054
  6. Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase.
    J Appl Microbiol. 1999 Aug;87(2):289-93 PMID: 10475971
  7. Somatic mutations affect key pathways in lung adenocarcinoma.
    Nature. 2008 Oct 23;455(7216):1069-75 PMID: 18948947
  8. Super learner.
    Stat Appl Genet Mol Biol. 2007;6:Article25 PMID: 17910531
  9. A framework for variation discovery and genotyping using next-generation DNA sequencing data.
    Nat Genet. 2011 May;43(5):491-8 PMID: 21478889
  10. Dynamic regulation of PCNA ubiquitylation/deubiquitylation.
    FEBS Lett. 2011 Sep 16;585(18):2780-5 PMID: 21640107
  11. Understanding resistance to EGFR inhibitors-impact on future treatment strategies.
    Nat Rev Clin Oncol. 2010 Sep;7(9):493-507 PMID: 20551942
  12. A method and server for predicting damaging missense mutations.
    Nat Methods. 2010 Apr;7(4):248-9 PMID: 20354512
  13. Comprehensive molecular characterization of human colon and rectal cancer.
    Nature. 2012 Jul 18;487(7407):330-7 PMID: 22810696
  14. The Sequence Alignment/Map format and SAMtools.
    Bioinformatics. 2009 Aug 15;25(16):2078-9 PMID: 19505943
  15. mRNA and microRNA expression profiles of the NCI-60 integrated with drug activities.
    Mol Cancer Ther. 2010 May;9(5):1080-91 PMID: 20442302
  16. In vitro evaluation of dimethane sulfonate analogues with potential alkylating activity and selective renal cell carcinoma cytotoxicity.
    Mol Cancer Ther. 2004 Jul;3(7):849-60 PMID: 15252146
  17. Mutational inactivation of STAG2 causes aneuploidy in human cancer.
    Science. 2011 Aug 19;333(6045):1039-43 PMID: 21852505
  18. Fast and accurate short read alignment with Burrows-Wheeler transform.
    Bioinformatics. 2009 Jul 15;25(14):1754-60 PMID: 19451168
  19. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity.
    Nature. 2012 Mar 28;483(7391):603-7 PMID: 22460905
  20. The mutation spectrum revealed by paired genome sequences from a lung cancer patient.
    Nature. 2010 May 27;465(7297):473-7 PMID: 20505728
  21. DNMT3A mutations in acute myeloid leukemia.
    N Engl J Med. 2010 Dec 16;363(25):2424-33 PMID: 21067377
  22. Genotoxicity of tobacco smoke and tobacco smoke condensate: a review.
    Mutat Res. 2004 Nov;567(2-3):447-74 PMID: 15572290
  23. The consensus coding sequences of human breast and colorectal cancers.
    Science. 2006 Oct 13;314(5797):268-74 PMID: 16959974
  24. A gene expression database for the molecular pharmacology of cancer.
    Nat Genet. 2000 Mar;24(3):236-44 PMID: 10700175
  25. CHEK2 genomic and proteomic analyses reveal genetic inactivation or endogenous activation across the 60 cell lines of the US National Cancer Institute.
    Oncogene. 2012 Jan 26;31(4):403-18 PMID: 21765476
  26. Connecting genes, drugs and diseases.
    Nat Biotechnol. 2006 Nov;24(11):1365-6 PMID: 17093484
  27. MDM2 inhibitors for cancer therapy.
    Trends Mol Med. 2007 Jan;13(1):23-31 PMID: 17126603
  28. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data.
    Nucleic Acids Res. 2010 Sep;38(16):e164 PMID: 20601685
  29. Endogenous DNA replication stress results in expansion of dNTP pools and a mutator phenotype.
    EMBO J. 2012 Feb 15;31(4):895-907 PMID: 22234187
  30. The genomic complexity of primary human prostate cancer.
    Nature. 2011 Feb 10;470(7333):214-20 PMID: 21307934
  31. The NCI60 human tumour cell line anticancer drug screen.
    Nat Rev Cancer. 2006 Oct;6(10):813-23 PMID: 16990858
  32. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma.
    Science. 2010 Oct 8;330(6001):228-31 PMID: 20826764
  33. Exome sequencing identifies GRIN2A as frequently mutated in melanoma.
    Nat Genet. 2011 May;43(5):442-6 PMID: 21499247
  34. Haploview: analysis and visualization of LD and haplotype maps.
    Bioinformatics. 2005 Jan 15;21(2):263-5 PMID: 15297300
  35. DNA polymerase epsilon and delta proofreading suppress discrete mutator and cancer phenotypes in mice.
    Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17101-4 PMID: 19805137
  36. Predicting deleterious amino acid substitutions.
    Genome Res. 2001 May;11(5):863-74 PMID: 11337480
  37. Drug discovery: Cell lines battle cancer.
    Nature. 2012 Mar 28;483(7391):544-5 PMID: 22460893
  38. Comparison of in vitro anticancer-drug-screening data generated with a tetrazolium assay versus a protein assay against a diverse panel of human tumor cell lines.
    J Natl Cancer Inst. 1990 Jul 4;82(13):1113-8 PMID: 2359137
  39. CellMiner: a web-based suite of genomic and pharmacologic tools to explore transcript and drug patterns in the NCI-60 cell line set.
    Cancer Res. 2012 Jul 15;72(14):3499-511 PMID: 22802077
  40. Systematic identification of genomic markers of drug sensitivity in cancer cells.
    Nature. 2012 Mar 28;483(7391):570-5 PMID: 22460902
  41. A microRNA component of the p53 tumour suppressor network.
    Nature. 2007 Jun 28;447(7148):1130-4 PMID: 17554337
  42. Circuit diagrams for biological networks.
    Mol Syst Biol. 2006;2:2006.0002 PMID: 16738549
  43. Chemosensitivity prediction by transcriptional profiling.
    Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10787-92 PMID: 11553813
  44. Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants.
    Nature. 2013 Jan 10;493(7431):216-20 PMID: 23201682
  45. DNA protein cross-links produced by NSC 652287, a novel thiophene derivative active against human renal cancer cells.
    Mol Pharmacol. 1999 Sep;56(3):478-84 PMID: 10462535
  46. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes.
    Nature. 2010 Jan 21;463(7279):360-3 PMID: 20054297
  47. Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells.
    Cancer Cell. 2004 Aug;6(2):129-37 PMID: 15324696
  48. Mutation analysis of 24 known cancer genes in the NCI-60 cell line set.
    Mol Cancer Ther. 2006 Nov;5(11):2606-12 PMID: 17088437
  49. Predisposition to cancer caused by genetic and functional defects of mammalian Atad5.
    PLoS Genet. 2011 Aug;7(8):e1002245 PMID: 21901109
  50. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma.
    Nature. 2011 Jan 27;469(7331):539-42 PMID: 21248752
Article Info
Journal
Cancer research
Abbr.
Cancer Res
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-12-3342
Published
2013-07-15
Epub
2013-00-15
Pages
4372-82
Language
English
Region
United States
NLM ID
2984705R
PMCID
PMC4893961
Subset
IM
Grants
NHLBI NIH HHS · UC2 HL103010 · United States
NHLBI NIH HHS · RC2 HL102926 · United States
NHLBI NIH HHS · HL-102924 · United States
NHLBI NIH HHS · RC2 HL102924 · United States
Intramural NIH HHS · Z99 CA999999 · United States
NHLBI NIH HHS · RC2 HL103010 · United States
NHLBI NIH HHS · HL-102923 · United States
NHLBI NIH HHS · RC2 HL102923 · United States
NHLBI NIH HHS · UC2 HL102926 · United States
NHLBI NIH HHS · UC2 HL102923 · United States
NHLBI NIH HHS · UC2 HL102924 · United States
NHLBI NIH HHS · RC2 HL102925 · United States
NHLBI NIH HHS · UC2 HL102925 · United States
External Links
PubMed source DOI: 10.1158/0008-5472.CAN-12-3342 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2