Abstract
BackgroundCell lines are commonly used in various kinds of biomedical research in the world. However, it remains uncertain whether genomic alterations existing in primary tumor tissues are represented in cell lines and whether cell lines carry cell line-specific genomic alterations. This study was performed to answer these questions.MethodsArray-based comparative genomic hybridization (CGH) was employed with 4030 bacterial artificial chromosomes (BACs) that cover the genome at 1.0 megabase resolution to analyze DNA copy number aberrations (DCNAs) in 35 primary breast tumors and 24 breast cancer cell lines. DCNAs were compared between these two groups. A tissue microdissection technique was applied to primary tumor tissues to reduce the contamination of samples by normal tissue components.ResultsThe average number of BAC clones with DCNAs was 1832 (45.3% of spotted clones) and 971 (24.9%) for cell lines and primary tumor tissues, respectively. Gains of 1q and 8q and losses of 8p, 11q, 16q and 17p were detected in >50% of primary cancer tissues. These aberrations were also frequently detected in cell lines. In addition to these alterations, the cell lines showed recurrent genomic alterations including gains of 5p14-15, 20q11 and 20q13 and losses of 4p13-p16, 18q12, 18q21, Xq21.1 and Xq26-q28 that were barely detected in tumor tissue specimens. These are considered to be cell line-specific DCNAs. The frequency of the HER2 amplification was high in both cell lines and tumor tissues, but it was statistically different between cell lines and primary tumors (P = 0.012); 41.3 ± 29.9% for the cell lines and 15.9 ± 18.6% for the tissue specimens.ConclusionsEstablished cell lines carry cell lines-specific DCNAs together with recurrent aberrations detected in primary tumor tissues. It must therefore be emphasized that cell lines do not always represent the genotypes of parental tumor tissues.
Highlights
Cell lines are commonly used in various kinds of biomedical research in the world
The comparison of genomic profiles obtained from cell lines with those from primary tumor tissues is one of the best ways to determine the difference in genomic aberrations between cell lines and primary tumor tissues and to identify recurrent celll lines-specific genomic aberrations
This study examined the DNA copy number aberrations (DCNAs) of 24 breast cancer cell lines and 35 primary breast cancer tissues using array-based comparative genomic hybridization
Summary
Cell lines are commonly used in various kinds of biomedical research in the world. it remains uncertain whether genomic alterations existing in primary tumor tissues are represented in cell lines and whether cell lines carry cell line-specific genomic alterations. Cancer cell lines are routinely used for various kinds of biomedical research under the assumption that cell lines reflect the genotypic and phenotypic characteristics of primary tumor tissues Such cell lines do not always faithfully represent genomic alterations and gene. Some of the genomic alterations detected in the cell lines are considered as a result of selective pressure to adapt to the culture conditions, while others may be just incidental [12,13] This theory raises an additional question in regard to whether there are genomic aberrations specific for cell lines, or in vitro-specific genomic aberrations. In this context, it is crucial to distinguish genomic aberrations in tumor tissues from the secondary changes with cultivation. The comparison of genomic profiles obtained from cell lines with those from primary tumor tissues is one of the best ways to determine the difference in genomic aberrations between cell lines and primary tumor tissues and to identify recurrent celll lines-specific genomic aberrations
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