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Molecular Cancer Research
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Cancer Genes and Genomics

Genomic Changes and Gene Expression Profiles Reveal That Established Glioma Cell Lines Are Poorly Representative of Primary Human Gliomas

Aiguo Li, Jennifer Walling, Yuri Kotliarov, Angela Center, Mary Ellen Steed, Susie J. Ahn, Mark Rosenblum, Tom Mikkelsen, Jean Claude Zenklusen and Howard A. Fine
Aiguo Li
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Jennifer Walling
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Yuri Kotliarov
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Angela Center
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Mary Ellen Steed
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Susie J. Ahn
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Mark Rosenblum
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Tom Mikkelsen
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Jean Claude Zenklusen
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Howard A. Fine
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DOI: 10.1158/1541-7786.MCR-07-0280 Published January 2008
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  • FIGURE 1.
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    FIGURE 1.

    Regions of chromosome amplification and deletion detected using DNAcopy package and CGHAnalytics software for (in order from left to right) A172, Hs683, T98G, U251, and U87 glioma cell lines across all chromosomes. Red, amplifications; green, deletions.

  • FIGURE 2.
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    FIGURE 2.

    Regions of loss of heterozygosity detected according to the genotype calls from GDAS software with a threshold of 6% for the probability of being homozygous for a given region for (in order from left to right) A172, Hs683, T98G, U251, and U87 glioma cell lines across all chromosomes. Green, loss of heterozygosity regions.

  • FIGURE 3.
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    FIGURE 3.

    Differences in genomic alterations and transcriptomic profiles between established cell lines and tumor samples. A. The spectrum of genomic aberrations found in a consensus (10% or more) of 83 glioblastoma samples, in 5 glioma cell lines, and in 10 nonglioma tumor cell lines. Red, amplifications; green, deletions. Chromosome labels are indicated using two shades of gray bars on the top of A for 100K SNP arrays and on the bottom of A for 10K SNP arrays. Eclipse, alterations commonly present in both glioma cell lines and in tumor samples; rectangular shape, unique alterations present only in cell lines or only in tumor samples. B. PCA of glioblastoma, established glioma cell lines, and nonglioma tumor cell lines. C. HC of glioblastoma, established glioma cell lines, and nonglioma tumor cell lines. GBM, primary gliomas; GCL, glioma cell lines (in vitro cultured); GCL_in vivo, U87 and U251 intracranial xenografts; NGTCL, nonglioma tumor cell lines.

  • FIGURE 4.
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    FIGURE 4.

    Results of GSEA for the phenotypes of glioblastomas and cell lines. A. Genes in significantly up-regulated gene sets in cell lines (red) in all data (gray). B. Genes in significantly up-regulated gene sets in glioblastoma (green) in all data (gray). C. Genes in significantly up-regulated gene sets in glioma representative pathways (yellow) in all data (gray). Data are transformed to reflect the expression value differences. D. Running enrichment scores for proteasome pathway in cell lines, the genes in the set as “hits” against the ranked list of genes (bottom) in the expression data set. E. Running enrichment scores for par1 signaling pathway in glioblastoma, the genes in the set as hits against the ranked list of genes (bottom) in the expression data set.

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  • Table 1.

    Summary of GSEA of Glioblastomas Compared with Established Cell Lines

    Gene setsGenesAll cell lines
    Glioma cell lines
    In vivo
    In vitro
    ESNom pESNom pNom pNom p
    BioCarta
        fatty_acid_metabolism25−0.5860.008*−0.5680.013*No†0.724
        badPathway22−0.4960.019‡−0.4580.034‡No†0.933
        dcPathway20−0.5250.028‡−0.4740.095No†0.505
        par1Pathway18−0.5300.106−0.6200.011*0.766
        calcineurinPathway18−0.5390.047‡−0.4930.145No†0.337
        nfatPathway52−0.3970.048‡−0.3580.144No†0.490
    Gene Ontology
        GPCRs_Class_B_Secretin-like24−0.4670.026‡−0.4800.016‡0.027‡No
    Exp. sig.
        cell_adhesionExp. sig.−0.4360.002*−0.3850.009*0.042‡No
        ANTI_CD44_up23−0.4830.049‡−0.3530.3970.023‡No
    STKE and others
        ST_adrenergic31−0.4470.068−0.4580.034‡No†0.21
        SIG_PIP3_signaling_in_B_lymphocytes35−0.4910.037‡−0.4280.1371No†0.133
    • Abbreviations: ES, enrichment score; Nom p, nominal P value; Exp. sig., expression signatures.

    • ↵* Nominal P value of <0.01.

    • ↵† Gene set is not in the list.

    • ↵‡ Nominal P value of <0.05.

  • Table 2.

    Summary of GSEA of Established Cell Lines Compared with Glioblastomas

    Gene setsSourcesGenesAll cell lines
    Glioma cell lines
    ESNom pESNom p
    Proteasome activities
        Proteasome_DegradationBioCarta310.7870*0.7870*
        proteasomePathwayBioCarta210.9020*0.8630.002†
    Cell cycle activities
        CR_cell_cycleExp. sig.770.5620.002†0.5100.051‡
        Cell_cyclena770.6150*0.5230.091
        cellcyclePathwayna210.5600.011†0.4130.283
        Purine_metabolismGenMapp810.4770*0.4140.029‡
        HTERT_upExp. sig.980.5630.017‡0.5580.036‡
    Mitochondrial activities
        PGCExp. sig.3390.4270.037‡0.4130.052‡
        MitochondrialExp. sig.3970.4560.054‡0.4020.141
    Others
        RAP_downExp. sig.1870.6060.015‡0.5700.05‡
        LEU_downExp. sig.1380.6090.016‡0.5320.105
        GLUT_downExp. sig.2490.5950.01†0.5420.078
    • Abbreviation: na, data source information not available.

    • ↵* Nominal P value of <0.001.

    • ↵† Nominal P value of <0.01.

    • ↵‡ Nominal P value of <0.05.

Additional Files

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Molecular Cancer Research: 6 (1)
January 2008
Volume 6, Issue 1
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Genomic Changes and Gene Expression Profiles Reveal That Established Glioma Cell Lines Are Poorly Representative of Primary Human Gliomas
Aiguo Li, Jennifer Walling, Yuri Kotliarov, Angela Center, Mary Ellen Steed, Susie J. Ahn, Mark Rosenblum, Tom Mikkelsen, Jean Claude Zenklusen and Howard A. Fine
Mol Cancer Res January 1 2008 (6) (1) 21-30; DOI: 10.1158/1541-7786.MCR-07-0280

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Genomic Changes and Gene Expression Profiles Reveal That Established Glioma Cell Lines Are Poorly Representative of Primary Human Gliomas
Aiguo Li, Jennifer Walling, Yuri Kotliarov, Angela Center, Mary Ellen Steed, Susie J. Ahn, Mark Rosenblum, Tom Mikkelsen, Jean Claude Zenklusen and Howard A. Fine
Mol Cancer Res January 1 2008 (6) (1) 21-30; DOI: 10.1158/1541-7786.MCR-07-0280
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