Breast cancer cell lines carry cell line-specific genomic alterations that are distinct from aberrations in breast cancer tissues: comparison of the CGH profiles between cancer cell lines and primary cancer tissues.
BACKGROUND
Cell 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.


METHODS
Array-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.


RESULTS
The 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.


CONCLUSIONS
Established 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.
Tsuji
Katumi
K
Department of Pathology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
Kawauchi
Shigeto
S
Saito
Soichiro
S
Furuya
Tomoko
T
Ikemoto
Kenzo
K
Nakao
Motonao
M
Yamamoto
Shigeru
S
Oka
Masaaki
M
Hirano
Takashi
T
Sasaki
Kohsuke
K
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D055028:Comparative Genomic Hybridization / Q000379:methods; D056915:DNA Copy Number Variations; D018744:DNA, Plant / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged
D018744:DNA, Plant