Transposable elements drive widespread expression of oncogenes in human cancers
| Autor: | Erica C. Pehrsson, Xiaoyun Xing, Zea Z. Dailey, David M. Zhang, Daofeng Li, Sungsu Kim, David O'Donnell, Ting Wang, Paula M. Godoy, Hyo Sik Jang, Nakul M. Shah, Jeffrey I. Gordon, Alan Y. Du |
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| Rok vydání: | 2019 |
| Předmět: |
Transposable element
Regulatory Sequences Nucleic Acid Biology medicine.disease_cause Article Cell Line Evolution Molecular 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Neoplasms Genetics medicine Humans Promoter Regions Genetic 030304 developmental biology 0303 health sciences Oncogene Mechanism (biology) HEK 293 cells Cancer Oncogenes DNA Methylation medicine.disease HEK293 Cells Regulatory sequence DNA methylation DNA Transposable Elements K562 Cells Carcinogenesis 030217 neurology & neurosurgery |
| Zdroj: | Nature genetics |
| ISSN: | 1546-1718 1061-4036 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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