Item Type: | Review |
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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 |
ISSN: | 2379-3708 |
Publisher: | American Society for Clinical Investigation |
Volume: | 3 |
Number: | 20 |
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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