RT Journal Article
T1 A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor.
A1 Sin-Chan, Patrick
A1 Mumal, Iqra
A1 Suwal, Tannu
A1 Ho, Ben
A1 Fan, Xiaolian
A1 Singh, Irtisha
A1 Du, Yuchen
A1 Lu, Mei
A1 Patel, Neilket
A1 Torchia, Jonathon
A1 Popovski, Dean
A1 Fouladi, Maryam
A1 Guilhamon, Paul
A1 Hansford, Jordan R
A1 Leary, Sarah
A1 Hoffman, Lindsey M
A1 Mulcahy Levy, Jean M
A1 Lassaletta, Alvaro
A1 Solano-Paez, Palma
A1 Rivas, Eloy
A1 Reddy, Alyssa
A1 Gillespie, G Yancey
A1 Gupta, Nalin
A1 Van Meter, Timothy E
A1 Nakamura, Hideo
A1 Wong, Tai-Tong
A1 Ra, Young-Shin
A1 Kim, Seung-Ki
A1 Massimi, Luca
A1 Grundy, Richard G
A1 Fangusaro, Jason
A1 Johnston, Donna
A1 Chan, Jennifer
A1 Lafay-Cousin, Lucie
A1 Hwang, Eugene I
A1 Wang, Yin
A1 Catchpoole, Daniel
A1 Michaud, Jean
A1 Ellezam, Benjamin
A1 Ramanujachar, Ramya
A1 Lindsay, Holly
A1 Taylor, Michael D
A1 Hawkins, Cynthia E
A1 Bouffet, Eric
A1 Jabado, Nada
A1 Singh, Sheila K
A1 Kleinman, Claudia L
A1 Barsyte-Lovejoy, Dalia
A1 Li, Xiao-Nan
A1 Dirks, Peter B
A1 Lin, Charles Y
A1 Mack, Stephen C
A1 Rich, Jeremy N
A1 Huang, Annie
K1 C19MC
K1 ETMR
K1 LIN28A
K1 MYCN
K1 brain tumor
K1 cell-cycle
K1 epigenetics
K1 microRNA
K1 super-enhancer
K1 therapeutics
AB 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.
YR 2019
FD 2019
LK http://hdl.handle.net/10668/14229
UL http://hdl.handle.net/10668/14229
LA en
DS RISalud
RD Aug 13, 2025