A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor
Sin-Chan, P
Mumal, I
Suwal, T
Ho, B
Fan, X
Singh, I
Du, Y
Lu, M
Patel, N
Torchia, J
Popovski, D
Fouladi, M
Guilhamon, P
Hansford, JR
Leary, S
Hoffman, LM
Mulcahy Levy, JM
Lassaletta, A
Solano-Paez, P
Rivas, E
Reddy, A
Gillespie, GY
Gupta, N
Van Meter, TE
Nakamura, H
Wong, TT
Ra, YS
Kim, SK
Massimi, L
Grundy, RG
Fangusaro, J
Johnston, D
Chan, J
Lafay-Cousin, L
Hwang, EI
Wang, Y
Catchpoole, D
Michaud, J
Ellezam, B
Ramanujachar, R
Lindsay, H
Taylor, MD
Hawkins, CE
Bouffet, E
Jabado, N
Singh, SK
Kleinman, CL
Barsyte-Lovejoy, D
Li, XN
Dirks, PB
Lin, CY
Mack, SC
Rich, JN
Huang, A
- Publication Type:
- Journal Article
- Citation:
- Cancer Cell, 2019, 36 (1), pp. 51 - 67.e7
- Issue Date:
- 2019-07-08
Closed Access
Filename | Description | Size | |||
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1-s2.0-S1535610819302934-main.pdf | Published Version | 4.55 MB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Sin-Chan, P | en_US |
dc.contributor.author | Mumal, I | en_US |
dc.contributor.author | Suwal, T | en_US |
dc.contributor.author | Ho, B | en_US |
dc.contributor.author | Fan, X | en_US |
dc.contributor.author | Singh, I | en_US |
dc.contributor.author | Du, Y | en_US |
dc.contributor.author | Lu, M | en_US |
dc.contributor.author | Patel, N | en_US |
dc.contributor.author | Torchia, J | en_US |
dc.contributor.author | Popovski, D | en_US |
dc.contributor.author | Fouladi, M | en_US |
dc.contributor.author | Guilhamon, P | en_US |
dc.contributor.author | Hansford, JR | en_US |
dc.contributor.author | Leary, S | en_US |
dc.contributor.author | Hoffman, LM | en_US |
dc.contributor.author | Mulcahy Levy, JM | en_US |
dc.contributor.author | Lassaletta, A | en_US |
dc.contributor.author | Solano-Paez, P | en_US |
dc.contributor.author | Rivas, E | en_US |
dc.contributor.author | Reddy, A | en_US |
dc.contributor.author | Gillespie, GY | en_US |
dc.contributor.author | Gupta, N | en_US |
dc.contributor.author | Van Meter, TE | en_US |
dc.contributor.author | Nakamura, H | en_US |
dc.contributor.author | Wong, TT | en_US |
dc.contributor.author | Ra, YS | en_US |
dc.contributor.author | Kim, SK | en_US |
dc.contributor.author | Massimi, L | en_US |
dc.contributor.author | Grundy, RG | en_US |
dc.contributor.author | Fangusaro, J | en_US |
dc.contributor.author | Johnston, D | en_US |
dc.contributor.author | Chan, J | en_US |
dc.contributor.author | Lafay-Cousin, L | en_US |
dc.contributor.author | Hwang, EI | en_US |
dc.contributor.author | Wang, Y | en_US |
dc.contributor.author | Catchpoole, D | en_US |
dc.contributor.author | Michaud, J | en_US |
dc.contributor.author | Ellezam, B | en_US |
dc.contributor.author | Ramanujachar, R | en_US |
dc.contributor.author | Lindsay, H | en_US |
dc.contributor.author | Taylor, MD | en_US |
dc.contributor.author | Hawkins, CE | en_US |
dc.contributor.author | Bouffet, E | en_US |
dc.contributor.author | Jabado, N | en_US |
dc.contributor.author | Singh, SK | en_US |
dc.contributor.author | Kleinman, CL | en_US |
dc.contributor.author | Barsyte-Lovejoy, D | en_US |
dc.contributor.author | Li, XN | en_US |
dc.contributor.author | Dirks, PB | en_US |
dc.contributor.author | Lin, CY | en_US |
dc.contributor.author | Mack, SC | en_US |
dc.contributor.author | Rich, JN | en_US |
dc.contributor.author | Huang, A | en_US |
dc.date.available | 2019-06-03 | en_US |
dc.date.issued | 2019-07-08 | en_US |
dc.identifier.citation | Cancer Cell, 2019, 36 (1), pp. 51 - 67.e7 | en_US |
dc.identifier.issn | 1535-6108 | en_US |
dc.identifier.uri | http://hdl.handle.net/10453/137382 | |
dc.description.abstract | © 2019 Elsevier Inc. Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. Our data show that this powerful oncogenic circuit, which entraps an early neural lineage network, is potently abrogated by bromodomain inhibitor JQ1, leading to ETMR cell death. Sin-Chan et al. uncover a C19MC-LIN28A-MYCN super-enhancer-dependent oncogenic circuit in embryonal tumors with multilayered rosettes (ETMRs). The circuit entraps an early neural lineage network to sustain embryonic epigenetic programming and is vulnerable to bromodomain inhibition, which promotes ETMR cell death. | en_US |
dc.relation.ispartof | Cancer Cell | en_US |
dc.relation.isbasedon | 10.1016/j.ccell.2019.06.002 | en_US |
dc.subject.classification | Oncology & Carcinogenesis | en_US |
dc.title | A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor | en_US |
dc.type | Journal Article | |
utslib.citation.volume | 1 | en_US |
utslib.citation.volume | 36 | en_US |
utslib.for | 0604 Genetics | en_US |
utslib.for | 1112 Oncology and Carcinogenesis | en_US |
utslib.for | 1109 Neurosciences | en_US |
pubs.embargo.period | Not known | en_US |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Engineering and Information Technology | |
utslib.copyright.status | closed_access | |
pubs.issue | 1 | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 36 | en_US |
Abstract:
© 2019 Elsevier Inc. Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. Our data show that this powerful oncogenic circuit, which entraps an early neural lineage network, is potently abrogated by bromodomain inhibitor JQ1, leading to ETMR cell death. Sin-Chan et al. uncover a C19MC-LIN28A-MYCN super-enhancer-dependent oncogenic circuit in embryonal tumors with multilayered rosettes (ETMRs). The circuit entraps an early neural lineage network to sustain embryonic epigenetic programming and is vulnerable to bromodomain inhibition, which promotes ETMR cell death.
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