Variation in RNA expression and genomic DNA content acquired during cell culture

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 exa...

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Vydané v:	British journal of cancer Ročník 90; číslo 2; s. 476 - 482
Hlavní autori:	Hiorns, L R, Bradshaw, T D, Skelton, L A, Yu, Q, Kelland, L R, Leyland-Jones, B
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	London Nature Publishing Group UK 26.01.2004 Nature Publishing Group
Predmet:	Biological and medical sciences Biomedicine Breast cancer Breast Neoplasms - genetics Breast Neoplasms - pathology Cancer Research Cell culture Cell Culture Techniques Chromosome Aberrations DNA, Neoplasm - analysis Drug Resistance Epidemiology Female Female genital diseases Gene expression Genetics and Genomics Genomic Instability Gynecology. Andrology. Obstetrics Humans Laboratories Mammary gland diseases Medical research Medical sciences Molecular Medicine Nucleic Acid Hybridization Oligonucleotide Array Sequence Analysis Oncology Ovarian cancer Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Reproducibility of Results Tumor Cells, Cultured Tumors United Kingdom > UK breast cancer expression arrays CGH cell culture ovarian cancer Cell culture RNA Acquired Ovary cancer DNA chip Variations Breast cancer Malignant tumor Gene expression Female genital diseases Mammary gland diseases Ovarian diseases Chromosome DNA breast cancer ovarian cancer
ISSN:	0007-0920, 1532-1827
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0007-0920 1532-1827
DOI:	10.1038/sj.bjc.6601405