Analysis of p53 mutation status in human cancer cell lines - A paradigm for cell line cross-contamination

Cancer cell lines are essential tools used in many areas of biomedical research. Using the last release of the UMD_p53 database (2007) (http://p53.free.fr), we analysed the p53 status of 1,211 cell lines published between 1989 and 2007. p53 mutations in cell lines from various types of cancers display a striking similarity in the distribution of mutations and in the pattern of mutational events compared to tumours, indicating that they are representative of the cells from which they were derived. Analysis of the residual transcriptional activity of p53 mutants identified in cell lines that displayed two different p53 mutations show that there is a high frequency of weak mutations that are paired with more potent mutations suggesting a driver/passenger configuration. Strikingly, we found discrepancies in the p53 status for 23% (88/384) of cell lines, for which the p53 status was established independently in two laboratories. Using the NCI-60 cell line panel as a model widely used in the literature, the p53 status could not be ascertained for 13 cell lines due to a lack of homogeneous data in the literature. Our study clearly confirms that misidentified cell lines are still a silent and neglected danger and that extreme care should be taken as a wrong p53 status could lead to disastrous experimental interpretations. The p53 web site has been updated with new sections describing the p53 status in the majority of cell lines and a special section devoted to cell lines with controversial p53 status.