Oncogenesis in transgenic and knockout mice

In order to treat and prevent cancer we must first understand how the activation of oncogenes and the loss of tumor suppressors play a role in tumorigenesis. Thus, the ability to accurately model cancer in a multicellular organism brings great insight to the questions surrounding tumor growth and treatment in humans. The ability to model cancer in multicellular organisms was a tremendous breakthrough in cancer research and manipulation of the mouse genome made a large impact in this field. It is now possible to model human cancer in the mouse by overexpressing oncogenes or inactivating tumor suppressor genes. New approaches in this field have improved the accuracy of modeling somatic cancer in the mouse and analyzing the genomic instability that occurs in murine tumors. Such models have provided much of our in vivo understanding of cancer. This chapter discusses how retroviral gene delivery, chromosome engineering, and inducible transgenes have been used to manipulate the mouse genome in a more precise spatial and temporal pattern. New tools for tumor analysis such as spectral karyotyping, fluorescence in situ hybridization and comparative genome hybridization have improved our ability to detect chromosomal rearrangements, while microarray analysis generates global expression patterns to decipher complex gene patterns that occur in cancers.We have attempted to highlight methodologies that have resulted in the improvement of genetic manipulation of the mouse with respect to tumorigenesis, as well as tools developed to demonstrated and analyze these tumors.