Genetic variability in a frozen batch of MCF-7 cells invisible in routine authentication affecting cell function

Andre Kleensang, Marguerite M. Vantangoli, Shelly Odwin-Dacosta, Melvin E. Andersen, Kim Boekelheide, Mounir Bouhifd, Albert J. Fornace, Heng Hong Li, Carolina B. Livi, Samantha Madnick, Alexandra Maertens, Michael Rosenberg, James D Yager, Liang Zhaog, Thomas Hartung

Research output: Contribution to journalArticle

Abstract

Common recommendations for cell line authentication, annotation and quality control fall short addressing genetic heterogeneity. Within the Human Toxome Project, we demonstrate that there can be marked cellular and phenotypic heterogeneity in a single batch of the human breast adenocarcinoma cell line MCF-7 obtained directly from a cell bank that are invisible with the usual cell authentication by short tandem repeat (STR) markers. STR profiling just fulfills the purpose of authentication testing, which is to detect significant cross-contamination and cell line misidentification. Heterogeneity needs to be examined using additional methods. This heterogeneity can have serious consequences for reproducibility of experiments as shown by morphology, estrogenic growth dose-response, whole genome gene expression and untargeted mass-spectroscopy metabolomics for MCF-7 cells. Using Comparative Genomic Hybridization (CGH), differences were traced back to genetic heterogeneity already in the cells from the original frozen vials from the same ATCC lot, however, STR markers did not differ from ATCC reference for any sample. These findings underscore the need for additional quality assurance in Good Cell Culture Practice and cell characterization, especially using other methods such as CGH to reveal possible genomic heterogeneity and genetic drifts within cell lines.

Original languageEnglish (US)
Article number28994
JournalScientific Reports
Volume6
DOIs
StatePublished - Jul 26 2016

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MCF-7 Cells
Microsatellite Repeats
Cell Line
Comparative Genomic Hybridization
Genetic Heterogeneity
Genetic Drift
Metabolomics
Quality Control
Mass Spectrometry
Adenocarcinoma
Breast
Cell Culture Techniques
Genome
Gene Expression
Growth

ASJC Scopus subject areas

  • General

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Genetic variability in a frozen batch of MCF-7 cells invisible in routine authentication affecting cell function. / Kleensang, Andre; Vantangoli, Marguerite M.; Odwin-Dacosta, Shelly; Andersen, Melvin E.; Boekelheide, Kim; Bouhifd, Mounir; Fornace, Albert J.; Li, Heng Hong; Livi, Carolina B.; Madnick, Samantha; Maertens, Alexandra; Rosenberg, Michael; Yager, James D; Zhaog, Liang; Hartung, Thomas.

In: Scientific Reports, Vol. 6, 28994, 26.07.2016.

Research output: Contribution to journalArticle

Kleensang, A, Vantangoli, MM, Odwin-Dacosta, S, Andersen, ME, Boekelheide, K, Bouhifd, M, Fornace, AJ, Li, HH, Livi, CB, Madnick, S, Maertens, A, Rosenberg, M, Yager, JD, Zhaog, L & Hartung, T 2016, 'Genetic variability in a frozen batch of MCF-7 cells invisible in routine authentication affecting cell function', Scientific Reports, vol. 6, 28994. https://doi.org/10.1038/srep28994
Kleensang, Andre ; Vantangoli, Marguerite M. ; Odwin-Dacosta, Shelly ; Andersen, Melvin E. ; Boekelheide, Kim ; Bouhifd, Mounir ; Fornace, Albert J. ; Li, Heng Hong ; Livi, Carolina B. ; Madnick, Samantha ; Maertens, Alexandra ; Rosenberg, Michael ; Yager, James D ; Zhaog, Liang ; Hartung, Thomas. / Genetic variability in a frozen batch of MCF-7 cells invisible in routine authentication affecting cell function. In: Scientific Reports. 2016 ; Vol. 6.
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