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Transposable elements drive widespread expression of oncogenes in human cancers
Hyo Sik Jang1,2, Nakul M Shah1,2, Alan Y Du1,2
1Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.
Nature Genetics
|March 31, 2019
Summary
Transposable elements (TEs) can activate oncogenes in cancer through onco-exaptation. This study reveals TEs are a prevalent mechanism driving oncogene activation and tumorigenesis across many cancer types.
Area of Science:
- Genomics
- Cancer Biology
- Epigenetics
Background:
- Transposable elements (TEs) are abundant genetic sequences with regulatory potential.
- Epigenetic reactivation of TEs in cancer, termed onco-exaptation, can influence oncogenesis.
- The scope of TE onco-exaptation across diverse cancer types remains largely unknown.
Purpose of the Study:
- To comprehensively investigate the prevalence and impact of TE onco-exaptation events in human cancers.
- To identify specific TE-driven oncogene activation events and their regulatory mechanisms.
Main Methods:
- Analysis of 7,769 tumor and 625 normal datasets spanning 15 distinct cancer types.
- Identification of TE cryptic promoter-activation events linked to oncogene expression.
- Functional interrogation of a candidate TE-oncogene interaction (AluJb-LIN28B).
Main Results:
- Identified 129 TE cryptic promoter-activation events involving 106 oncogenes in 3,864 tumors.
- Demonstrated that genetic deletion of a TE abolished oncogene expression.
- Showcased dynamic DNA methylation modulating TE promoter activity for oncogene activation.
Conclusions:
- TE onco-exaptation is a widespread phenomenon contributing to oncogene dysregulation in cancer.
- TEs represent a significant and previously underappreciated mechanism for promiscuous oncogene activation.
- Understanding TE onco-exaptation is crucial for comprehending tumorigenesis and developing novel therapeutic strategies.
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