An oncogenic Kras expression signature identified by cross-species

Mouse lung cancers were generated using the KrasLA model, in which a latent mutated Kras2 allele (resulting in the amino acid substitution G12D) is sporadically activated through spontaneous homologous recombination. These mice develop lung adenomas with full penetrance; over time, the tumors acquire morphologic characteristics reminiscent of those of human adenocarcinoma, such as nuclear atypia and a high mitotic index. KrasLA2 mice on a 129svJae background were crossed with wild type C57B/6J mice to obtain F1 progeny. The initial report of this mouse model described two alleles, KrasLA1 and KrasLA2. All expression profiles in this study were generated using the KrasLA2 mice. We call the model KrasLA throughout for simplicity. Mice bearing the KrasLA latent allele were allowed to develop to 5-6 month of age and sacrificed by cervical dislocation. Lungs were removed and placed in RNAlaterTM solution (Ambion). Individual tumors large enough to be easily dissected (3mm-8mm) were removed and cut into 2 pieces. One piece was placed in formalin to be used for histological analysis while the other piece was stored at -80 for RNA/DNA extraction. Gene expression profiling was perfomed on lung tumors derived from KrasLA mouse (n = 31) and normal mouse lung samples (n = 19).