Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors
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Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors. / Torchia, Jonathon; Golbourn, Brian; Feng, Shengrui; Ho, King Ching; Sin-Chan, Patrick; Vasiljevic, Alexandre; Norman, Joseph D; Guilhamon, Paul; Garzia, Livia; Agamez, Natalia R; Lu, Mei; Chan, Tiffany S; Picard, Daniel; de Antonellis, Pasqualino; Khuong-Quang, Dong-Anh; Planello, Aline C; Zeller, Constanze; Barsyte-Lovejoy, Dalia; Lafay-Cousin, Lucie; Letourneau, Louis; Bourgey, Mathieu; Yu, Man; Gendoo, Deena M A; Dzamba, Misko; Barszczyk, Mark; Medina, Tiago; Riemenschneider, Alexandra N; Morrissy, A Sorana; Ra, Young-Shin; Ramaswamy, Vijay; Remke, Marc; Dunham, Christopher P; Yip, Stephen; Ng, Ho-Keung; Lu, Jian-Qiang; Mehta, Vivek; Albrecht, Steffen; Pimentel, Jose; Chan, Jennifer A; Somers, Gino R; Faria, Claudia C; Roque, Lucia; Fouladi, Maryam; Hoffman, Lindsey M; Moore, Andrew S; Wang, Yin; Choi, Seung Ah; Hansford, Jordan R; Catchpoole, Daniel; Birks, Diane K; Foreman, Nicholas K; Strother, Doug; Klekner, Almos; Bognár, Laszló; Garami, Miklós; Hauser, Péter; Hortobágyi, Tibor; Wilson, Beverly; Hukin, Juliette; Carret, Anne-Sophie; Van Meter, Timothy E; Hwang, Eugene I; Gajjar, Amar; Chiou, Shih-Hwa; Nakamura, Hideo; Toledano, Helen; Fried, Iris; Fults, Daniel; Wataya, Takafumi; Fryer, Chris; Eisenstat, David D; Scheinemann, Katrin; Fleming, Adam J; Johnston, Donna L; Michaud, Jean; Zelcer, Shayna; Hammond, Robert; Afzal, Samina; Ramsay, David A; Sirachainan, Nongnuch; Hongeng, Suradej; Larbcharoensub, Noppadol; Grundy, Richard G; Lulla, Rishi R; Fangusaro, Jason R; Druker, Harriet; Bartels, Ute; Grant, Ronald; Malkin, David; McGlade, C Jane; Nicolaides, Theodore; Tihan, Tarik; Phillips, Joanna; Majewski, Jacek; Montpetit, Alexandre; Bourque, Guillaume; Bader, Gary D; Reddy, Alyssa T; Gillespie, G Yancey; Warmuth-Metz, Monika; Rutkowski, Stefan; Tabori, Uri; Lupien, Mathieu; Brudno, Michael; Schüller, Ulrich; Pietsch, Torsten; Judkins, Alexander R; Hawkins, Cynthia E; Bouffet, Eric; Kim, Seung-Ki; Dirks, Peter B; Taylor, Michael D; Erdreich-Epstein, Anat; Arrowsmith, Cheryl H; De Carvalho, Daniel D; Rutka, James T; Jabado, Nada; Huang, Annie.
in: CANCER CELL, Jahrgang 30, Nr. 6, 12.12.2016, S. 891-908.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors
AU - Torchia, Jonathon
AU - Golbourn, Brian
AU - Feng, Shengrui
AU - Ho, King Ching
AU - Sin-Chan, Patrick
AU - Vasiljevic, Alexandre
AU - Norman, Joseph D
AU - Guilhamon, Paul
AU - Garzia, Livia
AU - Agamez, Natalia R
AU - Lu, Mei
AU - Chan, Tiffany S
AU - Picard, Daniel
AU - de Antonellis, Pasqualino
AU - Khuong-Quang, Dong-Anh
AU - Planello, Aline C
AU - Zeller, Constanze
AU - Barsyte-Lovejoy, Dalia
AU - Lafay-Cousin, Lucie
AU - Letourneau, Louis
AU - Bourgey, Mathieu
AU - Yu, Man
AU - Gendoo, Deena M A
AU - Dzamba, Misko
AU - Barszczyk, Mark
AU - Medina, Tiago
AU - Riemenschneider, Alexandra N
AU - Morrissy, A Sorana
AU - Ra, Young-Shin
AU - Ramaswamy, Vijay
AU - Remke, Marc
AU - Dunham, Christopher P
AU - Yip, Stephen
AU - Ng, Ho-Keung
AU - Lu, Jian-Qiang
AU - Mehta, Vivek
AU - Albrecht, Steffen
AU - Pimentel, Jose
AU - Chan, Jennifer A
AU - Somers, Gino R
AU - Faria, Claudia C
AU - Roque, Lucia
AU - Fouladi, Maryam
AU - Hoffman, Lindsey M
AU - Moore, Andrew S
AU - Wang, Yin
AU - Choi, Seung Ah
AU - Hansford, Jordan R
AU - Catchpoole, Daniel
AU - Birks, Diane K
AU - Foreman, Nicholas K
AU - Strother, Doug
AU - Klekner, Almos
AU - Bognár, Laszló
AU - Garami, Miklós
AU - Hauser, Péter
AU - Hortobágyi, Tibor
AU - Wilson, Beverly
AU - Hukin, Juliette
AU - Carret, Anne-Sophie
AU - Van Meter, Timothy E
AU - Hwang, Eugene I
AU - Gajjar, Amar
AU - Chiou, Shih-Hwa
AU - Nakamura, Hideo
AU - Toledano, Helen
AU - Fried, Iris
AU - Fults, Daniel
AU - Wataya, Takafumi
AU - Fryer, Chris
AU - Eisenstat, David D
AU - Scheinemann, Katrin
AU - Fleming, Adam J
AU - Johnston, Donna L
AU - Michaud, Jean
AU - Zelcer, Shayna
AU - Hammond, Robert
AU - Afzal, Samina
AU - Ramsay, David A
AU - Sirachainan, Nongnuch
AU - Hongeng, Suradej
AU - Larbcharoensub, Noppadol
AU - Grundy, Richard G
AU - Lulla, Rishi R
AU - Fangusaro, Jason R
AU - Druker, Harriet
AU - Bartels, Ute
AU - Grant, Ronald
AU - Malkin, David
AU - McGlade, C Jane
AU - Nicolaides, Theodore
AU - Tihan, Tarik
AU - Phillips, Joanna
AU - Majewski, Jacek
AU - Montpetit, Alexandre
AU - Bourque, Guillaume
AU - Bader, Gary D
AU - Reddy, Alyssa T
AU - Gillespie, G Yancey
AU - Warmuth-Metz, Monika
AU - Rutkowski, Stefan
AU - Tabori, Uri
AU - Lupien, Mathieu
AU - Brudno, Michael
AU - Schüller, Ulrich
AU - Pietsch, Torsten
AU - Judkins, Alexander R
AU - Hawkins, Cynthia E
AU - Bouffet, Eric
AU - Kim, Seung-Ki
AU - Dirks, Peter B
AU - Taylor, Michael D
AU - Erdreich-Epstein, Anat
AU - Arrowsmith, Cheryl H
AU - De Carvalho, Daniel D
AU - Rutka, James T
AU - Jabado, Nada
AU - Huang, Annie
N1 - Copyright © 2016 Elsevier Inc. All rights reserved.
PY - 2016/12/12
Y1 - 2016/12/12
N2 - We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.
AB - We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRTs and identify subgroup-specific therapeutic targets. We found ATRTs segregated into three epigenetic subgroups with distinct genomic profiles, SMARCB1 genotypes, and chromatin landscape that correlated with differential cellular responses to a panel of signaling and epigenetic inhibitors. Significantly, we discovered that differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype.
U2 - 10.1016/j.ccell.2016.11.003
DO - 10.1016/j.ccell.2016.11.003
M3 - SCORING: Journal article
C2 - 27960086
VL - 30
SP - 891
EP - 908
JO - CANCER CELL
JF - CANCER CELL
SN - 1535-6108
IS - 6
ER -