NCI-60 whole exome sequencing and pharmacological CellMiner analyses

Exome sequencing provides unprecedented insights into cancer biology and pharmacological response. Here we assess these two parameters for the NCI-60, which is among the richest genomic and pharmacological publicly available cancer cell line databases. Homozygous genetic variants that putatively aff...

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Bibliographic Details
Published in:PloS one 2014-07, Vol.9 (7), p.e101670-e101670
Main Authors: Reinhold, William C, Varma, Sudhir, Sousa, Fabricio, Sunshine, Margot, Abaan, Ogan D, Davis, Sean R, Reinhold, Spencer W, Kohn, Kurt W, Morris, Joel, Meltzer, Paul S, Doroshow, James H, Pommier, Yves
Format: Article
Language:English
Subjects:
Analysis
Antineoplastic Agents - pharmacology
Apoptosis
Base Sequence
Bioinformatics
Biology and Life Sciences
Cancer
Cell Line, Tumor
Cell lines
Computational Biology - methods
Computer and Information Sciences
Correlation
Data bases
Data Mining - methods
Databases, Factual
Deoxyribonucleic acid
DNA
DNA methylation
DNA repair
Drug approval
Epidermal growth factor receptors
ErbB-2 protein
Exome - genetics
Extracellular signal-regulated kinase
Gene expression
Genes
Genetic diversity
Genetic variance
Genetic Variation - genetics
Genetics
Genome - genetics
Genomes
Genomics
Genomics - methods
Humans
Identification
Ifosfamide
Insulin-like growth factors
Ionizing radiation
Kinases
Medical research
MicroRNAs
Mutation
Neoplasms - drug therapy
Neoplasms - genetics
Pharmacology
Rad52 protein
Research and Analysis Methods
Sequence Analysis, DNA
Stat2 protein
TOR protein
TSC2 protein
Tuberous Sclerosis Complex 2
Tumors
Visualization
Web sites
Websites
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Description
Summary:Exome sequencing provides unprecedented insights into cancer biology and pharmacological response. Here we assess these two parameters for the NCI-60, which is among the richest genomic and pharmacological publicly available cancer cell line databases. Homozygous genetic variants that putatively affect protein function were identified in 1,199 genes (approximately 6% of all genes). Variants that are either enriched or depleted compared to non-cancerous genomes, and thus may be influential in cancer progression and differential drug response were identified for 2,546 genes. Potential gene knockouts are made available. Assessment of cell line response to 19,940 compounds, including 110 FDA-approved drugs, reveals ≈80-fold range in resistance versus sensitivity response across cell lines. 103,422 gene variants were significantly correlated with at least one compound (at p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0101670