title: High resolution copy number variation data in the NCI-60 cancer cell lines from whole genome microarrays accessible through CellMiner.
abstract: Array-based comparative genomic hybridization (aCGH) is a powerful technique for detecting gene copy number variation. It is generally considered to be robust and convenient since it measures DNA rather than RNA. In the current study, we combine copy number estimates from four different platforms (Agilent 44 K, NimbleGen 385 K, Affymetrix 500 K and Illumina Human1Mv1_C) to compute a reliable, high-resolution, easy to understand output for the measure of copy number changes in the 60 cancer cells of the NCI-DTP (the NCI-60). We then relate the results to gene expression. We explain how to access that database using our CellMiner web-tool and provide an example of the ease of comparison with transcript expression, whole exome sequencing, microRNA expression and response to 20,000 drugs and other chemical compounds. We then demonstrate how the data can be analyzed integratively with transcript expression data for the whole genome (26,065 genes). Comparison of copy number and expression levels shows an overall medium high correlation (median r = 0.247), with significantly higher correlations (median r = 0.408) for the known tumor suppressor genes. That observation is consistent with the hypothesis that gene loss is an important mechanism for tumor suppressor inactivation. An integrated analysis of concurrent DNA copy number and gene expression change is presented. Limiting attention to focal DNA gains or losses, we identify and reveal novel candidate tumor suppressors with matching alterations in transcript level.
authors.affiliation: Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America; HiThru Analytics LLC, Laurel, Maryland, United States of America.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Varma
authors.affiliation: Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.affiliation: Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America; Systems Research and Applications Corporation, Fairfax, Virginia, United States of America.
authors.forename: Margot
authors.initials: M
authors.lastname: Sunshine
authors.affiliation: Departments of Bioinformatics and Computational Biology and Department of Systems Biology, M.D. Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: John N
authors.initials: JN
authors.lastname: Weinstein
authors.affiliation: Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: William C
authors.initials: WC
authors.lastname: Reinhold
mesh_terms: D045744:Cell Line, Tumor; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics*; D042822:Genomic Instability; D006801:Humans; D020407:Internet; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012984:Software; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins