Knock-in of oncogenic mutations in human somatic cells as a tool to identify genoselective compounds

摘要: C126 Cellular models are widely used to investigate the oncogenic properties of genetic alterations and assess effects antineoplastic agents. We have created novel somatic 9 knock-in9 cell-lines for several common cancer alterations. exploited AAV-mediated homologous recombination introduce frequently found mutations in genome non transformed human cells, thus closely recapitulating their genesis tumors. Heterozygous mutant cells displayed distinct allele-specific biochemical biological 9gain-of-function9 but, surprisingly, were not transformed. Profiling clinically approved compounds on mutated retrieved established previously unknown mutation-specific drug sensitization profiles pharmacological clusters. Thus, knock-in defines new cellular study tumor progression provides a pharmaco-genomic platform discovery.