Chromosomal Abnormalities, Cancer and Mouse Models The Critical Role of Translocation-Associated Genes in Human Cancer

Cancer results from subversion of the processes that control the normal growth, location and mortality of cells. This loss of normal control mechanisms arises from the acquisition of mutations in three broad categories of genes proto-oncogenes, tumor suppressor genes and DNA repair enzymes. Proto-oncogene activation may occur by mutation, gene amplification or DNA rearrangement. Chromosomal translocations entail the generation of gene fusions in both haematopoietic and solid mesenquimal tumors. Despite the successful identification of these specific and consistent genetic events, the nature of the intimate association between the gene fusion and the resulting phenotype is pending to understand. The application of transgenic methods to the study of these cancer-associated gene fusions have provided insights into their in vivo functions and suggested mechanisms by which lineage selection may be achieved. Herein these studies are reviewed to illustrate how manipulation of their loci in the mouse has contributed to current understanding in unique and unexpected ways.