The tumor pathology of genetically engineered mice: Genomic pathology

This chapter examines a newly emerging view of tumorigenesis by exploring the evidence that the molecular origin of the tumor determines the microscopic phenotype of the tumor. It is primarily based on the genetically engineered mice (GEM) expressing transgenic oncogenes or lacking homologs of human tumor-suppressor genes. The current data supporting this hypothesis are based primarily on mouse models of human prostate and breast cancers, but additional evidence is provided from other organ systems. The data demonstrate that the molecular origins of tumors create unique signature phenotypes that belong to distinct molecular pathways. The members of each pathway display unique interrelationships and dependencies. Many of the signature phenotypes mimic human tumor morphology in incredible detail and often represent involvement of the same genes. The pathology of tumorigenesis in GEM has important implications for human and comparative pathology.