Cell lines missidentification and TP53 mutations
TP53 status effects the phenotype of tumor cell lines profoundly and must be carefully ascertained for any experimental project. Despite numerous warnings, the misidentification of cell lines is still present as a silent and neglected issue, and that extreme care must be taken when determining the status of p53, because errors may lead to disastrous experimental interpretations.
In 2008 we published a first report describing the status of TP53 mutation in cell lines. We were highly concerned by the finding that many cell lines had controversial TP53 status, including popular cell lines such as those from the NCI-60 panels.
Berglind, H., Pawitan, Y., Kato, S., Ishioka, C., and Soussi, T. (2008). Analysis of p53 mutation status in human cancer cell lines: a paradigm for cell line cross-contamination.
Cancer Biol Ther 7, 699-708
In 2014, the situation has not really progressed despite efforts from the scientific community to raise awareness and encourage the provision of accurate data. A few journals have begun to tackle this problem and require cell line authentication before publication.
Leroy, B., Girard, L., Minna, J. D., Gazdar, A. F., and Soussi, T. (2014). Analysis of p53 mutation status in human cancer cell lines: a reassessment.
Hum Mutat 35, 456-465.
A comparison of two of the most prominent cancer genome sequencing databases from different institutes (Cancer Cell Line Encyclopedia and Catalogue of Somatic Mutations in Cancer) revealed marked discrepancies in the detection of missense mutations in identical cell lines (57.38% conformity)
see Hudson et al for more information
Hudson AM, Yates T, Li Y, Trotter EW, Fawdar S, Chapman P, Lorigan P, Biankin A, Miller CJ, Brognard J (2014) Discrepancies in cancer genomic sequencing highlight opportunities for driver mutation discovery. Cancer Res 74: 6390-6396.
The p53 Mutations in Cell Lines compendium
The p53 Mutations in Cell Lines compendium is a novel and original application that provides an ID card for each cell line included in the UMD TP53 database. The current version includes 2,000 and 500 cell lines with mutant TP53 and wild-type TP53 respectively.
The ID cards include cell line data such as cancer type and ATCC number when available, as well as some specific information on potential misidentifications, changes of identity or shared origins with other cell lines. A first set of information focuses on the TP53 mutation and provides data on the various properties of the protein mutant, e.g., its frequency in the database, the consequences of the mutation on TP53 activities as predicted by the most common algorithms or its residual activities assessed using a yeast functional assay. A second set of information depicts the consequences of this mutation on the various transcripts and isoforms expressed by the TP53 gene using the official HGVS description (http://www.hgvs.org/) and the TP53 coordinates and nomenclature recommended by the Locus Reference Genomic (http://www.lrg-sequence.org/).