Genetically engineered mice can provide unique insights critical to understanding tumor biology. They can be used to validate the role of genes found mutated in cancer. Also, they provide a great preclinical tool to test drug efficacy against tumor specific targets. Here we propose to interrogate the entire genome of our myeloma prone mice to identify mutations (genomic amplifications or deletions) that cause rapid growth of the myeloma cells. Candidate gene will then be inserted in the genome of our myeloma prone mice to validate their contribution to tumor progression. We expect the identification of these genes in the mouse will give us novel clues to pathways important in human myeloma tumorigenesis.