BIOINFORMATICS ANALYSIS OF MUTATION PROFILES SUGGESTS LIMITATIONS OF STABILIZED CELL LINES IN TESTING ANTICANCER DRUGS


Stoczynska-Fidelus E., Bienkowski M., Piaskowski S., Pacholczyk M., Winiecka M. and Rieske P.

Department of Tumour Biology, Medical University of Lodz, Poland


Abstract:


Although many data question the adequacy of using cell lines for drug testing, they are frequently used as in vitro models. To this end, we compared genetic characterization of thousands of cell lines (in vitro) and surgery samples (in vivo) described in COSMIC (Catalogue Of Somatic Mutations In Cancer) Database and Cancer Cell Line Encyclopedia (CCLE). Histopathological diagnosis was included. Our analysis suggests completely different genetic characterization of cell lines vs. surgery samples. We observed absence of single heterozygous mutations of many suppressor genes in vitro and high frequency of these mutations in vivo. Similarly, cell lines show higher percentage of tumor suppressors nonsense mutations. Many other discrepancies were statistically significant.  We suggest that stabilized neoplastic cell lines bias many aspects of cancer cells biology and show only part of possible responses to antineoplastic drugs.

This study was supported by the National Science Center Grant No. 2011/01/B/NZ4/07832.