Large-scale genomic efforts to study human
cancer, such as the cancer gene atlas (TCGA), have identified numerous
cancer drivers in a wide variety of
tumor types. However, there are limitations to this approach, the mutations and expression or copy number changes that are identified are not always clearly functionally relevant, and only annotated genes and genetic elements are thoroughly queried. The use of complimentary, nonbiased, functional approaches to identify drivers of
cancer development and progression is ideal to maximize the rate at which
cancer discoveries are achieved. One such approach that has been successful is the use of the Sleeping Beauty (SB) transposon-based mutagenesis system in mice. This system uses a conditionally expressed
transposase and mutagenic transposon allele to target mutagenesis to somatic cells of a given tissue in mice to cause random mutations leading to
tumor development. Analysis of
tumors for transposon common insertion sites (CIS) identifies candidate cancer genes specific to that
tumor type. While similar screens have been performed in mice with the PiggyBac (PB) transposon and viral approaches, we limit extensive discussion to SB. Here we discuss the basic structure of these screens, screens that have been performed, methods used to identify CIS.