Gene expression profiles of spontaneous metastasis in a K-ras/p53 mutant mouse model. Mus musculus

The biologic basis for NSCLC metastasis is not well understood. Here we addressed this deficiency by transcriptionally profiling tumors from a genetic mouse model of human lung adenocarcinoma that develops metastatic disease owing to the expression of K-rasG12D and p53R172H. We identified 2,209 genes that were differentially expressed in distant metastases relative to matched lung tumors. Mining of publicly available data bases revealed this expression signature in a subset of NSCLC patients who had a poorer prognosis than those without the signature. Overall design: Primary lung adenocarcinomas and metastases from p53R172H∆g/+ K-rasLA1/+ mice or syngeneic tumors were isolated, carefully dissected to remove the adjacent tissue, snap-frozen in liquid nitrogen and stored at -80° until use. Part of each dissected tumor was histologically evaluated by a board-certified pathologist. Synthesis of cRNA and hybridization to Mouse Expression Array 430A 2.0 chips were performed. Two-sided t-paired tests using log-transformed expression values determined significant differences between primary tumors and metastasis.