Genomic changes and gene expression profiles reveal that established glioma cell lines are poorly representative of primary human gliomas.
Genetic aberrations, such as gene amplification, deletions, and loss of heterozygosity, are hallmarks of cancer and are thought to be major contributors to the neoplastic process. Established cancer cell lines have been the primary in vitro and in vivo models for cancer for more than 2 decades; however, few such cell lines have been extensively characterized at the genomic level. Here, we present a high-resolution genome-wide chromosomal alteration and gene expression analyses of five of the most commonly used glioma cell lines and compare the findings with those observed in 83 primary human gliomas. Although genomic alterations known to occur in primary tumors were identified in the cell lines, we also observed several novel recurrent aberrations in the glioma cell lines that are not frequently represented in primary tumors. Additionally, a global gene expression cluster distinct from primary tumors was identified in the glioma cell lines. Our results indicate that established cell lines are generally a poor representation of primary tumor biology, presenting a host of genomic and gene expression changes not observed in primary tissues, although some discrete features of glioma biology were conserved in the established cell lines. Refined maps of genetic alterations and transcriptional divergence from the original tumor type, such as the one presented here, may help serve as a guideline for a more biologically rational and clinically relevant selection of the most appropriate glioma model for a given experiment.
Li
Aiguo
A
Neuro-Oncology Branch, National Cancer Institute, National Institutes of Neurological Disorder and Stroke, NIH, Bethesda, MD 20892, USA.
Walling
Jennifer
J
Kotliarov
Yuri
Y
Center
Angela
A
Steed
Mary Ellen
ME
Ahn
Susie J
SJ
Rosenblum
Mark
M
Mikkelsen
Tom
T
Zenklusen
Jean Claude
JC
Fine
Howard A
HA
D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D002877:Chromosomes, Human / Q000235:genetics; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D015894:Genome, Human / Q000235:genetics*; D005838:Genotype; D005909:Glioblastoma / Q000235:genetics; D005910:Glioma / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D010641:Phenotype; D012984:Software