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Emerging functions of DNA transposases and oncogenic mutators in childhood cancer development

Item Type:Review
Title:Emerging functions of DNA transposases and oncogenic mutators in childhood cancer development
Creators Name:Henssen, A.G. and Kentsis, A.
Abstract:Our understanding of the molecular pathogenesis of childhood cancers has advanced substantially, but their fundamental causes remain poorly understood. Recently, multiple mechanisms of DNA damage and repair have been associated with mutations observed in human cancers. Here, we review the physiologic functions and oncogenic activities of transposable genetic elements. In particular, we focus on the recent studies implicating DNA transposases RAG1/2 and PGBD5 as oncogenic mutators that promote genomic rearrangements in childhood leukemias and solid tumors. We outline future studies that will be needed to define the contributions of transposons to mutational processes that become dysregulated in cancer cells. In addition, we discuss translational approaches, including synthetic lethal strategies, for identifying and developing improved clinical therapies to target oncogenic transposons and transposases.
Keywords:Carcinogenesis, DNA Damage, DNA Repair, DNA Transposable Elements, Gene Rearrangement, Mutation, Neoplasms, Transposases
Source:JCI Insight
Publisher:American Society for Clinical Investigation
Page Range:123172
Date:18 October 2018
Official Publication:https://doi.org/10.1172/jci.insight.123172
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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