Transposable elements drive widespread expression of oncogenes in human cancers

Hyo Sik Jang; Nakul M. Shah; Alan Y. Du; Zea Z. Dailey; Erica C. Pehrsson; Paula M. Godoy; David Zhang; Daofeng Li; Xiaoyun Xing; Sungsu Kim; David O’Donnell; Jeffrey I. Gordon; Ting Wang

doi:10.1038/s41588-019-0373-3

Transposable elements drive widespread expression of oncogenes in human cancers

Hyo Sik Jang, Nakul M. Shah, Alan Y. Du, Zea Z. Dailey, Erica C. Pehrsson, Paula M. Godoy, David Zhang, Daofeng Li, Xiaoyun Xing, Sungsu Kim, David O’Donnell, Jeffrey I. Gordon, Ting Wang

Research output: Contribution to journal › Letter › peer-review

240 Scopus citations

Abstract

Transposable elements (TEs) are an abundant and rich genetic resource of regulatory sequences^1–3. 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.

Original language	English
Pages (from-to)	611-617
Number of pages	7
Journal	Nature Genetics
Volume	51
Issue number	4
DOIs	https://doi.org/10.1038/s41588-019-0373-3
State	Published - Apr 1 2019

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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 = "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",

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T1 - Transposable elements drive widespread expression of oncogenes in human cancers

AU - Jang, Hyo Sik

AU - Shah, Nakul M.

AU - Du, Alan Y.

AU - Dailey, Zea Z.

AU - Pehrsson, Erica C.

AU - Godoy, Paula M.

AU - Zhang, David

AU - Li, Daofeng

AU - Xing, Xiaoyun

AU - Kim, Sungsu

AU - O’Donnell, David

AU - Gordon, Jeffrey I.

AU - Wang, Ting

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41588-019-0373-3

M3 - Letter

C2 - 30926969

AN - SCOPUS:85063919967

SN - 1061-4036

VL - 51

SP - 611

EP - 617

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Transposable elements drive widespread expression of oncogenes in human cancers

Abstract

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