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Nat Genet. 2019 Apr;51(4):611-617. doi: 10.1038/s41588-019-0373-3. Epub 2019 Mar 29.

Transposable elements drive widespread expression of oncogenes in human cancers.

Jang HS1,2, Shah NM1,2, Du AY1,2, Dailey ZZ1,2, Pehrsson EC1,2, Godoy PM1,2, Zhang D1,2, Li D1,2, Xing X1,2, Kim S1,3, O'Donnell D1,2,4, Gordon JI1,2,4, Wang T5,6.

Author information

1
Department of Genetics, Washington University School of Medicine, St Louis, MO, USA.
2
The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA.
3
Hope Center for Neurological Disease, Washington University School of Medicine, St Louis, MO, USA.
4
Center for Gut Microbiome and Nutrition Research, Washington University School of Medicine, St Louis, MO, USA.
5
Department of Genetics, Washington University School of Medicine, St Louis, MO, USA. twang@wustl.edu.
6
The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St Louis, MO, USA. twang@wustl.edu.

Abstract

Transposable elements (TEs) are an abundant and rich genetic resource of regulatory sequences1-3. Cryptic regulatory elements within TEs can be epigenetically reactivated in cancer to influence oncogenesis in a process termed onco-exaptation4. However, the prevalence and impact of TE onco-exaptation events across cancer types are poorly characterized. Here, we analyzed 7,769 tumors and 625 normal datasets from 15 cancer types, identifying 129 TE cryptic promoter-activation events involving 106 oncogenes across 3,864 tumors. Furthermore, we interrogated the AluJb-LIN28B candidate: the genetic deletion of the TE eliminated oncogene expression, while dynamic DNA methylation modulated promoter activity, illustrating the necessity and sufficiency of a TE for oncogene activation. Collectively, our results characterize the global profile of TE onco-exaptation and highlight this prevalent phenomenon as an important mechanism for promiscuous oncogene activation and ultimately tumorigenesis.

PMID:
30926969
PMCID:
PMC6443099
DOI:
10.1038/s41588-019-0373-3
[Indexed for MEDLINE]
Free PMC Article

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