Cancer Gene Discovery Using the Sleeping Beauty Essay

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[Cell Cycle 4:12, 1744-1748, December 2005]; ©2005 Landes Bioscience Cancer Gene Discovery Using the Sleeping Beauty Transposon Perspective Timothy K. Starr David A. Largaespada* ABSTRACT Epidemiological and molecular data support the hypothesis that cancer results from a series of acquired somatic mutations. Discovering the initial mutations required for oncogenesis has long been a goal of cancer research. To date, the majority of causative mutations have been identified based on their ability to act in a dominant fashion and/or because they are activated by chromosomal translocations. Forward genetic screens are necessary for unbiased discovery of the remaining unknown oncogenic mutations. Two recent projects have demonstrated the feasibility of using the Sleeping Beauty transposon as an insertional mutagen for cancer gene discovery. In this article we discuss the history of cancer gene discovery and propose novel forward genetic screens using Sleeping Beauty transposon aimed at specific tissues and accelerating the discovery of recessive tumor suppressor genes. Received 10/04/05; Accepted 10/05/05 Sleeping Beauty, cancer, mutagenesis screen, transposon, cancer genetics, oncogenesis © 20 05 LA ND ES BIO SC IEN CE .D SB Sleeping Beauty TSG tumor suppressor gene Sixty years after Peyton Rous first demonstrated that an entity smaller than a bacterium can cause cancer,1 Robert Huebner and George Todaro made the hypothesis that activation of dormant viral oncogenes causes cancer.2 In the next decade, the gene responsible for the phenomenon observed by Rous was identified as the avian viral oncogene, Src,3,4 which, surprisingly at the time, was also found in the genome of uninfected birds.5 This lead to the hypothesis that oncogenes are mutated versions of normal “proto-oncogenes”, which was supported by the

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