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

Anton G Henssen1,2,3, Alex Kentsis4,5

  • 1Department of Pediatric Oncology/Hematology, Charité-Universitätsmedizin, Berlin, Germany.

JCI Insight
|October 19, 2018
PubMed

Insights

Transposable genetic elements, specifically DNA transposases RAG1/2 and PGBD5, act as oncogenic mutators. These elements promote genomic rearrangements in childhood cancers, highlighting new therapeutic targets.

Area of Science:

  • Genetics
  • Molecular Biology
  • Oncology

Background:

  • Childhood cancer pathogenesis is complex, with fundamental causes often unclear.
  • DNA damage and repair mechanisms are increasingly linked to cancer mutations.
  • Transposable genetic elements (transposons) have recognized physiological roles and potential oncogenic activities.

Purpose of the Study:

  • To review the oncogenic roles of transposable genetic elements, focusing on DNA transposases RAG1/2 and PGBD5.
  • To highlight their implication in promoting genomic rearrangements in pediatric leukemias and solid tumors.
  • To outline future research directions and translational therapeutic strategies.

Main Methods:

  • Literature review of recent studies on transposable elements and cancer.
  • Focus on the role of RAG1/2 and PGBD5 as oncogenic mutators.
  • Discussion of potential therapeutic strategies, including synthetic lethality.

Main Results:

  • DNA transposases RAG1/2 and PGBD5 are implicated as oncogenic mutators.
  • These transposases promote genomic rearrangements in various childhood cancers.
  • Transposons contribute to dysregulated mutational processes in cancer cells.

Conclusions:

  • Transposons and their associated enzymes play a significant role in childhood cancer development.
  • Further research is needed to fully understand transposon contributions to cancer mutational processes.
  • Targeting oncogenic transposons and transposases offers potential for novel clinical therapies.

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