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, Bognar, Laszlo, Garami, Miklos, Hauser, Peter, Hortobagyi, 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, Schuller, 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 and Huang, Annie (2016) Integrated (epi)-genomic analyses identify subgroup-specific therapeutic targets in CNS rhabdoid tumors. Cancer Cell, 30 6: 891-908. doi:10.1016/j.ccell.2016.11.003

Author 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
Bognar, Laszlo
Garami, Miklos
Hauser, Peter
Hortobagyi, 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
Schuller, 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
Title Integrated (epi)-genomic analyses identify subgroup-specific therapeutic targets in CNS rhabdoid tumors
Journal name Cancer Cell   Check publisher's open access policy
ISSN 1878-3686
Publication date 2016-12-12
Sub-type Article (original research)
DOI 10.1016/j.ccell.2016.11.003
Open Access Status Not yet assessed
Volume 30
Issue 6
Start page 891
End page 908
Total pages 18
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Formatted abstract
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.
Keyword ATRT
Rhabdoid tumors
Subgroup-specific therapeutics
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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