Variation in RNA expression and genomic DNA content acquired during cell culture
Open accessAbstract
Specific chromosomal abnormalities are increasingly recognised to be associated with particular tumour subtypes. These cytogenetic abnormalities define the sites of specific genes, the alteration of which is implicated in the neoplastic process. We used comparative genomic hybridisation (CGH) to examine DNA from different breast and ovarian cancer cell lines for variations in DNA sequence copy number compared with the same normal control. We also compared different sources of the MCF7 breast line by both CGH and cDNA expression arrays. Some of the differences between the subcultures were extensive and involved large regions of the chromosome. Differences between the four subcultures were observed for gains of 2q, 5p, 5q, 6q, 7p, 7q, 9q, 10p, 11q, 13q, 14q, 16q, 18p and 20p, and losses of 4q, 5p, 5q, 6q, 7q, 8p, 11p, 11q, 12q, 13q, 15q, 19p, 19q, 20p, 21q, 22q and Xp. However, few variations were found between two subcultures examined, 5 months apart, from the same initial source. The RNA arrays also demonstrated considerable variation between the three different subcultures, with only 43% of genes expressed at the same levels in all three. Moreover, the patterns of the expressed genes did not always reflect our observed CGH aberrations. These results demonstrate extensive genomic instability and variation in RNA expression during subculture and provide supportive data for evidence that cell lines do evolve in culture, thereby weakening the direct relevance of such cultures as models of human cancer. This work also reinforces the concern that comparisons of published analyses of cultures of the same name may be dangerous.
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Cell model heterogeneity can weaken the direct relevance of such cultures as models of human cancer and makes inter-laboratory reproduction of experimental findings difficult.
“But such heterogeneity can most certainly be a curse when it comes to other common applications of such cells, as it not only weakens “the direct relevance of such cultures as models of human cancer”8 but also “makes inter-laboratory reproduction of experimental findings difficult”24.”
From Genetic variability in a frozen batch of MCF-7 cells invisible in routine authentication affecting cell function (2016) · cites this paper as [8]
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- Authors
- Hiorns, L. R., Bradshaw, T. D., Skelton, L. A., Yu, Q., Kelland, L. R., & Leyland-Jones, B.
- Affiliations
- St Bartholomew's Hospital (GB)
- University of Nottingham (GB)
- Institute of Cancer Research (GB)
- McGill University (CA)
- Corresponding author
- Leyland-Jones, B
- ORCID
- Bradshaw, T D
- Venue
- British Journal of Cancer
- Published
- 2004-01
- Volume
- 90
- Issue
- 2
- Pages
- 476-482
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- PMC
- PMC2409579
- OpenAlex
- W2079023951
- Cited by
- 32
- References
- 26
- Citations by year
- 2023: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2016: 4 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- www.springer.com/tdm (unspecified)
- Locations
- British Journal of Cancer (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- genomic instability, DNA copy number alterations, chromosomal abnormalities, gene expression variation, breast cancer cell lines, ovarian cancer cell lines, MCF-7 cells, comparative genomic hybridization
- MeSH terms
- Breast Neoplasms, Chromosome Aberrations, DNA, Neoplasm, Female, Humans, Nucleic Acid Hybridization, Ovarian Neoplasms, Tumor Cells, Cultured, Reproducibility of Results, Cell Culture Techniques, Oligonucleotide Array Sequence Analysis, Genomic Instability
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