Abstract
The use of transposons as insertional mutagens to identify cancer genes in mice has generated a wealth of information over the past decade. Here, we discuss recent major advances in transposon-mediated insertional mutagenesis screens and compare this technology with other screening strategies.
Highlights
Genome sequencing has revealed a plethora of mutations in cancer, with some tumors carrying tens of thousands of somatic mutations [1]
The PB screen identified candidate drivers that had been identified by the pancreatic Sleeping Beauty (SB) screen as well as novel candidate pancreatic cancer genes, and exemplified the complementarity of the SB and PB approaches as in vivo insertional mutagens for cancer gene discovery. Another consideration that investigators should be mindful of when performing insertional mutagenesis screens is the damage done to the genome by the process of transposition itself as transposons are mobilized from chromosomal integration sites
In a SB-mediated transposon-mediated insertional mutagenesis (TMIM) screen aimed at identifying genes that co-operate with oncogenic B-Raf in melanoma development, a significant enrichment of genes was discovered among the Common insertion site (CIS) that encode mRNAs with the ability to regulate the expression of the tumor suppressor Pten [48]
Summary
Genome sequencing has revealed a plethora of mutations in cancer, with some tumors carrying tens of thousands of somatic mutations [1]. The first insertional mutagenesis efforts in mice were performed with the murine leukemia virus and the mouse mammary transforming virus to induce lymphoma and mammary tumors [2, 3], respectively, and led to the identification of numerous cancer pathways, including the WNT pathway [4]. These viruses were found to be of limited utility for mutagenesis in other tissue types owing to viral tropism and the fact. We discuss recent advances in cancer gene discovery using transposons and their role in the era of other mutagenesis tools such as clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)
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