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JCI Insight. 2018 Oct 18;3(20). pii: 123172. doi: 10.1172/jci.insight.123172. [Epub ahead of print]

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

Author information

1
Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin, Berlin, Germany.
2
German Cancer Consortium, Berlin, Germany.
3
Berlin Institute of Health, Berlin, Germany.
4
Departments of Pediatrics, Pharmacology, and Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York, USA.
5
Sloan Kettering Institute, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.

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.

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