Transposons for cancer gene discovery Sleeping Beauty and beyond 英文参考文献.docVIP

Review Transposons for cancer gene discovery: Sleeping Beauty and beyond Lara S Collier and David A Largaespada The Department of Genetics, Cell Biology and Development, The Cancer Center, The University of Minnesota Twin Cities, Church St SE, Minneapolis, Minnesota 55455, USA Correspondence: Lara S Collier. E-mail: lsc5e@ Published: 31 October 2007 Genome Biology 2007, 8(Suppl 1):S15 (doi:10.1186/gb-2007-8-S1-S15) The electronic version of this article is the complete one and can be found online at /2007/8/S1/S15 ? 2007 BioMed Central Ltd Abstract The use of Sleeping Beauty transposons as somatic mutagens to discover cancer genes in hematopoietic tumors and sarcomas has been documented. Here, we discuss the future of Sleeping Beauty for cancer genetic studies and the potential use of additional transposable elements for somatic mutagenesis. Introduction used as powerful insertional somatic mutagens for cancer gene discovery in mice, as well as other laboratory animals, for many years [6-10]. Despite the important discoveries made, retroviruses have several limitations that the use of nonviral insertional mutagens, such as SB, are expected to overcome [5]. Cancer genomes are complex, and there are probably many yet undiscovered tumor suppressor genes (TSGs) and onco- genes. The multiple mechanisms by which cancer genes can suffer mutation, including amplification/deletion, point mutation, and epigenetic silencing, can complicate cancer gene discovery. Forward genetic approaches for cancer gene discovery are attractive because they allow unbiased, whole genome scans for cancer genes. In mice, treatment with chemical and radiologic mutagens can mutate cancer genes and promote tumor formation, but identification of the affected gene is difficult and is often achieved using a candidate gene approach. The use of insertional mutagens