Agilent Technologies Inc. (NYSE: A) today announced that scientists using the company's comparative genomic hybridization (CGH) technology have shown that cancer cell lines, which are broadly used in all aspects of biomedical research, may have vast differences in their genetic makeup, even when grown in the same batch.
As a result, the scientists have recommended that cell culture banks use advanced genomic technologies, such as array CGH, to ensure the consistency of the cells they provide to the research community.
Researchers have long been aware that some popular cell lines are not stable. That is, their biological properties and genetic makeup change as cultures are propagated in laboratories. While standard precautions and quality assurance methods are being used to control such changes and validate authenticity of the cell lines, they may not be sufficient, according to a paper published July 26 in Scientific Reports, an online journal from the publishers of Nature.
A consortium of scientists from Agilent, Brown University, Georgetown University, Hamner Institutes and Johns Hopkins Bloomberg School of Public Health has been engaged in a multi-year study that aims to develop a new generation of assays for testing environmental toxicity. The study, known as the Human Toxome Project, combines multiple "-omic" technologies and bioinformatics.
The scientists, led by Dr. Thomas Hartung of Johns Hopkins, selected the well-established breast cancer cell line MCF-7, known to be prone to spontaneous rearrangements, as their model system. In an effort to establish reproducibility, they conducted cell culture work in two independent sites using identical laboratory protocols. They obtained the MCF-7 cells from the same cell bank and lot numbers, meaning they were grown in the same batch. Cells were validated using standard methods at the cell bank and at the project sites. However, despite extensive efforts to synchronize their protocols, the scientists were unable to obtain comparable results at the two sites.
They accumulated cytological, transcript profiling and phenotypic evidence that the cells were actually different. Of particular importance, they found that the cells demonstrated vastly different responses to induction by the natural human hormone estrogen: one of the two cell lines was hypersensitive to estrogen, the other was not.
Using CGH technology from Agilent, the scientists confirmed that the two cell lines had vast differences in their genetic makeup, in some cases as large as entire human chromosomes.
The authors of the research paper concluded that existing methods for assuring the quality of cell cultures are insufficient. They recommended that advanced genomic technologies, such as array CGH, be broadly deployed by cell culture banks to ensure consistency of the cells they provide to the research community. For this project alone, the team estimated the additional costs of the unplanned experiments and delays to the project totaled around $1 million.
"Agilent's array CGH platform is a leading technology used in hundreds of genomic and cytogenetic laboratories worldwide," said Herman Verrelst, Agilent vice president and general manager of the company's Genomics Solutions Division and Clinical Applications Division. "We are pleased to see this example of using our technology to increase reproducibility of cell culture research. It is striking that a simple array CGH experiment, which would have cost less than $1,000 at a commercial service provider, could have prevented $1 million in lost research funding and several years of delay."
The paper, "Genetic Variability in a Frozen Batch of MCF-7 Cells Invisible in Routine Authentication Affecting Cell Function," was written by Andre Kleensang, Marguerite M. Vantangoli, Shelly Odwin-DaCosta, Melvin E. Andersen, Kim Boekelheide, Mounir Bouhifd, Albert J. Fornace Jr, Carolina B. Livi, Samantha Madnick, Alexandra Maertens, Michael Rosenberg, James D. Yager and Thomas Hartung.
The research was supported by a grant from the National Institutes of Health.