Engineering Large Genomic Rearrangement in Mouse Embryonic Stem Cell for Cancer Gene Discovery

Over the last several decades, multiple recurrent chromosomal amplifications and deletions have been detected in a large number of cancers. These regions of amplification and deletion can encompass a few to several hundred genes. Determining which of these genes is causing the outgrowth of the cancer is difficult. Complicating the analysis is the fact that several genes within the affected chromosomal region may cooperate to promote tumorigenesis. In this protocol we describe a method of chromosomal engineering in mice that allows modeling of chromosomal duplications and deficiencies. This method faithfully recapitulates several aspects of chromosomal loss and gain in human cancers and can reveal cancer drivers difficult to identify by other means.