Copy Number Alterations in Glioma Cell Lines

Established tumor-derived cell lines are widely and routinely used as in vitro cancer models for various kinds of biomedical research. The easy management of these cell cultures, in contrast to the inherent difficulty in establishing and mantaining primary tumoral cultures, has contributed to the wide use of these inmortalized cell lines in order to characterize the biological significance of specific genomic aberrations identified in primary tumors. Therefore, it has been assumed that the genomic and expression aberrations of long-term established cell lines resemble, and are representative, of the primary tumor from which the cell line was derived. Indeed, the cell line-based research has been performed, not only for the definition of the molecular biology of several cancer models, but also for the investigation of new targeted therapeutic agents in a prior step to clinical practice. The use of tumor-derived cell lines has been highly relevant for the testing and development of new therapeutical agents, with several cancer cell-line panels having been developed for drug sensitivity screening and new agents’ discovery (Sharma et al, 2010). Controversial concerning the ability of tumor-derived cell lines to accurately reflect the phenotype and genotype of the parental histology has been documented. A previous report of Greshock and coworkers using array-based Comparative Genomic Hybridization (aCGH) data of seven diagnosis-specific matched tumors and cell lines showed that, on average, cell lines preserve in vitro the genetic aberrations that are unique to the parent histology from which they were derived, while acquiring additional locus-specific alterations in long-term cultures (Greshock et al, 2007). In contrast, a study on breast cancer cell lines and primary tumors highlight that cell lines do not always represent the genotypes of parental tumor tissues (Tsuji et al, 2010). Furthermore, a parallel genomic and expression study on glioma cell lines and primary tumors states that in this specific cancer type, cell lines are poor representative of the primary tumors (Li et al, 2008). Given the importance of the use of cell lines as models for the study of the biology and development of tumors, and for the testing of the mode of action of new therapeutical agents, the knowledge of which genomic alterations are tumor-specific or which are necessary for the maintenance of the cell line in culture, becomes essential.