@article{3b473668587f4ffd857dfa97fd3ccc85,
title = "Transposable elements drive widespread expression of oncogenes in human cancers",
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.",
author = "Jang, {Hyo Sik} and Shah, {Nakul M.} and Du, {Alan Y.} and Dailey, {Zea Z.} and Pehrsson, {Erica C.} and Godoy, {Paula M.} and David Zhang and Daofeng Li and Xiaoyun Xing and Sungsu Kim and David O{\textquoteright}Donnell and Gordon, {Jeffrey I.} and Ting Wang",
note = "Funding Information: We would like to thank J. Hoisington-L{\'o}pez and M.L. Jaeger from The Edison Family Center for Genome Sciences & Systems Biology (CGSSB) for assistance with sequencing; B. Koebbe and E. Martin from CGSSB for data processing; M. Savio, M. Patana and D. Schweppe from the Siteman Flow Cytometry core for FACS-related expertise; M. Goodell and Y. Huang for valuable expertise with the SunTag-DNMT3A system and L. Maggi (Washington University School of Medicine) for generously gifting the H838 cell line. This work was funded by NIH grant numbers 5R01HG007175, U24ES026699 and U01HG009391 and the American Cancer Society Research Scholar grant number RSG-14-049-01-DMC. H.S.J. was supported by a grant from NIGMS (no. T32 GM007067). A.Y.D. is supported by a grant from NHGRI (no. T32 HG000045). N.M.S. is a Howard Hughes Medical Institute (H.H.M.I.) Medical Research Fellow, http://www.hhmi.org/. The xenograft work cited in this publication was performed in a facility supported by NCRR grant number C06 RR015502. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2019",
month = apr,
day = "1",
doi = "10.1038/s41588-019-0373-3",
language = "English",
volume = "51",
pages = "611--617",
journal = "Nature Genetics",
issn = "1061-4036",
number = "4",
}