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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, Vol. 30, No. 6, 12.12.2016, p. 891-908.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Torchia, J, Golbourn, B, Feng, S, Ho, KC, Sin-Chan, P, Vasiljevic, A, Norman, JD, Guilhamon, P, Garzia, L, Agamez, NR, Lu, M, Chan, TS, Picard, D, de Antonellis, P, Khuong-Quang, D-A, Planello, AC, Zeller, C, Barsyte-Lovejoy, D, Lafay-Cousin, L, Letourneau, L, Bourgey, M, Yu, M, Gendoo, DMA, Dzamba, M, Barszczyk, M, Medina, T, Riemenschneider, AN, Morrissy, AS, Ra, Y-S, Ramaswamy, V, Remke, M, Dunham, CP, Yip, S, Ng, H-K, Lu, J-Q, Mehta, V, Albrecht, S, Pimentel, J, Chan, JA, Somers, GR, Faria, CC, Roque, L, Fouladi, M, Hoffman, LM, Moore, AS, Wang, Y, Choi, SA, Hansford, JR, Catchpoole, D, Birks, DK, Foreman, NK, Strother, D, Klekner, A, Bognár, L, Garami, M, Hauser, P, Hortobágyi, T, Wilson, B, Hukin, J, Carret, A-S, Van Meter, TE, Hwang, EI, Gajjar, A, Chiou, S-H, Nakamura, H, Toledano, H, Fried, I, Fults, D, Wataya, T, Fryer, C, Eisenstat, DD, Scheinemann, K, Fleming, AJ, Johnston, DL, Michaud, J, Zelcer, S, Hammond, R, Afzal, S, Ramsay, DA, Sirachainan, N, Hongeng, S, Larbcharoensub, N, Grundy, RG, Lulla, RR, Fangusaro, JR, Druker, H, Bartels, U, Grant, R, Malkin, D, McGlade, CJ, Nicolaides, T, Tihan, T, Phillips, J, Majewski, J, Montpetit, A, Bourque, G, Bader, GD, Reddy, AT, Gillespie, GY, Warmuth-Metz, M, Rutkowski, S, Tabori, U, Lupien, M, Brudno, M, Schüller, U, Pietsch, T, Judkins, AR, Hawkins, CE, Bouffet, E, Kim, S-K, Dirks, PB, Taylor, MD, Erdreich-Epstein, A, Arrowsmith, CH, De Carvalho, DD, Rutka, JT, Jabado, N & Huang, A 2016, 'Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors', CANCER CELL, vol. 30, no. 6, pp. 891-908. https://doi.org/10.1016/j.ccell.2016.11.003

APA

Torchia, J., Golbourn, B., Feng, S., Ho, K. C., Sin-Chan, P., Vasiljevic, A., Norman, J. D., Guilhamon, P., Garzia, L., Agamez, N. R., Lu, M., Chan, T. S., Picard, D., de Antonellis, P., Khuong-Quang, D-A., Planello, A. C., Zeller, C., Barsyte-Lovejoy, D., Lafay-Cousin, L., ... Huang, A. (2016). Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors. CANCER CELL, 30(6), 891-908. https://doi.org/10.1016/j.ccell.2016.11.003

Vancouver

Torchia J, Golbourn B, Feng S, Ho KC, Sin-Chan P, Vasiljevic A et al. Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors. CANCER CELL. 2016 Dec 12;30(6):891-908. https://doi.org/10.1016/j.ccell.2016.11.003

Bibtex

@article{dabfeffc4c6643f8837c1e19ce57c961,
title = "Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors",
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.",
author = "Jonathon Torchia and Brian Golbourn and Shengrui Feng and Ho, {King Ching} and Patrick Sin-Chan and Alexandre Vasiljevic and Norman, {Joseph D} and Paul Guilhamon and Livia Garzia and Agamez, {Natalia R} and Mei Lu and Chan, {Tiffany S} and Daniel Picard and {de Antonellis}, Pasqualino and Dong-Anh Khuong-Quang and Planello, {Aline C} and Constanze Zeller and Dalia Barsyte-Lovejoy and Lucie Lafay-Cousin and Louis Letourneau and Mathieu Bourgey and Man Yu and Gendoo, {Deena M A} and Misko Dzamba and Mark Barszczyk and Tiago Medina and Riemenschneider, {Alexandra N} and Morrissy, {A Sorana} and Young-Shin Ra and Vijay Ramaswamy and Marc Remke and Dunham, {Christopher P} and Stephen Yip and Ho-Keung Ng and Jian-Qiang Lu and Vivek Mehta and Steffen Albrecht and Jose Pimentel and Chan, {Jennifer A} and Somers, {Gino R} and Faria, {Claudia C} and Lucia Roque and Maryam Fouladi and Hoffman, {Lindsey M} and Moore, {Andrew S} and Yin Wang and Choi, {Seung Ah} and Hansford, {Jordan R} and Daniel Catchpoole and Birks, {Diane K} and Foreman, {Nicholas K} and Doug Strother and Almos Klekner and Laszl{\'o} Bogn{\'a}r and Mikl{\'o}s Garami and P{\'e}ter Hauser and Tibor Hortob{\'a}gyi and Beverly Wilson and Juliette Hukin and Anne-Sophie Carret and {Van Meter}, {Timothy E} and Hwang, {Eugene I} and Amar Gajjar and Shih-Hwa Chiou and Hideo Nakamura and Helen Toledano and Iris Fried and Daniel Fults and Takafumi Wataya and Chris Fryer and Eisenstat, {David D} and Katrin Scheinemann and Fleming, {Adam J} and Johnston, {Donna L} and Jean Michaud and Shayna Zelcer and Robert Hammond and Samina Afzal and Ramsay, {David A} and Nongnuch Sirachainan and Suradej Hongeng and Noppadol Larbcharoensub and Grundy, {Richard G} and Lulla, {Rishi R} and Fangusaro, {Jason R} and Harriet Druker and Ute Bartels and Ronald Grant and David Malkin and McGlade, {C Jane} and Theodore Nicolaides and Tarik Tihan and Joanna Phillips and Jacek Majewski and Alexandre Montpetit and Guillaume Bourque and Bader, {Gary D} and Reddy, {Alyssa T} and Gillespie, {G Yancey} and Monika Warmuth-Metz and Stefan Rutkowski and Uri Tabori and Mathieu Lupien and Michael Brudno and Ulrich Sch{\"u}ller and Torsten Pietsch and Judkins, {Alexander R} and Hawkins, {Cynthia E} and Eric Bouffet and Seung-Ki Kim and Dirks, {Peter B} and Taylor, {Michael D} and Anat Erdreich-Epstein and Arrowsmith, {Cheryl H} and {De Carvalho}, {Daniel D} and Rutka, {James T} and Nada Jabado and Annie Huang",
note = "Copyright {\textcopyright} 2016 Elsevier Inc. All rights reserved.",
year = "2016",
month = dec,
day = "12",
doi = "10.1016/j.ccell.2016.11.003",
language = "English",
volume = "30",
pages = "891--908",
journal = "CANCER CELL",
issn = "1535-6108",
publisher = "Cell Press",
number = "6",

}

RIS

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 -