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.
KeywordsMammary Tumor Mouse Mammary Tumor Virus Prostatic Intraepithelial Neoplasia Islet Cell Tumor Granulosa Cell Tumor
Dr. Cardiff wrote and takes sole responsibility for the text. The author is indebted to Drs. A.D. Borowsky, J.M. Ward, M. Bosenberg, J. Longfellow, J. Arbeit, A.Y. Nikitin, S. Kogan, J.J. Galvez, K. Aldape, and others who provided the outlines for the systemic pathology. We appreciate the willingness of investigators who shared unpublished data and images with us. This work has been supported, in part, by grants and contracts R01 CA089140, 22XS037A, U01 CA10102, and U01 CA084294 from the National Cancer Institute and National Centers for Research Resources (UR42-RR1495) from the NIH.
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