Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors.
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
- Publisher:
- Elsevier BV
- Publication Type:
- Journal Article
- Citation:
- Cancer Cell, 2016, 30, (6), pp. 891-908
- Issue Date:
- 2016-12-12
Closed Access
Filename | Description | Size | |||
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PIIS1535610816305098.pdf | Published version | 8.39 MB | Adobe PDF |
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Torchia, J | |
dc.contributor.author | Golbourn, B | |
dc.contributor.author | Feng, S | |
dc.contributor.author | Ho, KC | |
dc.contributor.author | Sin-Chan, P | |
dc.contributor.author | Vasiljevic, A | |
dc.contributor.author | Norman, JD | |
dc.contributor.author | Guilhamon, P | |
dc.contributor.author | Garzia, L | |
dc.contributor.author | Agamez, NR | |
dc.contributor.author | Lu, M | |
dc.contributor.author | Chan, TS | |
dc.contributor.author | Picard, D | |
dc.contributor.author | de Antonellis, P | |
dc.contributor.author | Khuong-Quang, D-A | |
dc.contributor.author | Planello, AC | |
dc.contributor.author | Zeller, C | |
dc.contributor.author | Barsyte-Lovejoy, D | |
dc.contributor.author | Lafay-Cousin, L | |
dc.contributor.author | Letourneau, L | |
dc.contributor.author | Bourgey, M | |
dc.contributor.author | Yu, M | |
dc.contributor.author | Gendoo, DMA | |
dc.contributor.author | Dzamba, M | |
dc.contributor.author | Barszczyk, M | |
dc.contributor.author | Medina, T | |
dc.contributor.author | Riemenschneider, AN | |
dc.contributor.author | Morrissy, AS | |
dc.contributor.author | Ra, Y-S | |
dc.contributor.author | Ramaswamy, V | |
dc.contributor.author | Remke, M | |
dc.contributor.author | Dunham, CP | |
dc.contributor.author | Yip, S | |
dc.contributor.author | Ng, H-K | |
dc.contributor.author | Lu, J-Q | |
dc.contributor.author | Mehta, V | |
dc.contributor.author | Albrecht, S | |
dc.contributor.author | Pimentel, J | |
dc.contributor.author | Chan, JA | |
dc.contributor.author | Somers, GR | |
dc.contributor.author | Faria, CC | |
dc.contributor.author | Roque, L | |
dc.contributor.author | Fouladi, M | |
dc.contributor.author | Hoffman, LM | |
dc.contributor.author | Moore, AS | |
dc.contributor.author | Wang, Y | |
dc.contributor.author | Choi, SA | |
dc.contributor.author | Hansford, JR | |
dc.contributor.author |
Catchpoole, D |
|
dc.contributor.author | Birks, DK | |
dc.contributor.author | Foreman, NK | |
dc.contributor.author | Strother, D | |
dc.contributor.author | Klekner, A | |
dc.contributor.author | Bognár, L | |
dc.contributor.author | Garami, M | |
dc.contributor.author | Hauser, P | |
dc.contributor.author | Hortobágyi, T | |
dc.contributor.author | Wilson, B | |
dc.contributor.author | Hukin, J | |
dc.contributor.author | Carret, A-S | |
dc.contributor.author | Van Meter, TE | |
dc.contributor.author | Hwang, EI | |
dc.contributor.author | Gajjar, A | |
dc.contributor.author | Chiou, S-H | |
dc.contributor.author | Nakamura, H | |
dc.contributor.author | Toledano, H | |
dc.contributor.author | Fried, I | |
dc.contributor.author | Fults, D | |
dc.contributor.author | Wataya, T | |
dc.contributor.author | Fryer, C | |
dc.contributor.author | Eisenstat, DD | |
dc.contributor.author | Scheinemann, K | |
dc.contributor.author | Fleming, AJ | |
dc.contributor.author | Johnston, DL | |
dc.contributor.author | Michaud, J | |
dc.contributor.author | Zelcer, S | |
dc.contributor.author | Hammond, R | |
dc.contributor.author | Afzal, S | |
dc.contributor.author | Ramsay, DA | |
dc.contributor.author | Sirachainan, N | |
dc.contributor.author | Hongeng, S | |
dc.contributor.author | Larbcharoensub, N | |
dc.contributor.author | Grundy, RG | |
dc.contributor.author | Lulla, RR | |
dc.contributor.author | Fangusaro, JR | |
dc.contributor.author | Druker, H | |
dc.contributor.author | Bartels, U | |
dc.contributor.author | Grant, R | |
dc.contributor.author | Malkin, D | |
dc.contributor.author | McGlade, CJ | |
dc.contributor.author | Nicolaides, T | |
dc.contributor.author | Tihan, T | |
dc.contributor.author | Phillips, J | |
dc.contributor.author | Majewski, J | |
dc.contributor.author | Montpetit, A | |
dc.contributor.author | Bourque, G | |
dc.contributor.author | Bader, GD | |
dc.contributor.author | Reddy, AT | |
dc.contributor.author | Gillespie, GY | |
dc.contributor.author | Warmuth-Metz, M | |
dc.contributor.author | Rutkowski, S | |
dc.contributor.author | Tabori, U | |
dc.contributor.author | Lupien, M | |
dc.contributor.author | Brudno, M | |
dc.contributor.author | Schüller, U | |
dc.contributor.author | Pietsch, T | |
dc.contributor.author | Judkins, AR | |
dc.contributor.author | Hawkins, CE | |
dc.contributor.author | Bouffet, E | |
dc.contributor.author | Kim, S-K | |
dc.contributor.author | Dirks, PB | |
dc.contributor.author | Taylor, MD | |
dc.contributor.author | Erdreich-Epstein, A | |
dc.contributor.author | Arrowsmith, CH | |
dc.contributor.author | De Carvalho, DD | |
dc.contributor.author | Rutka, JT | |
dc.contributor.author | Jabado, N | |
dc.contributor.author | Huang, A | |
dc.date.accessioned | 2022-08-11T00:55:55Z | |
dc.date.available | 2016-10-31 | |
dc.date.available | 2022-08-11T00:55:55Z | |
dc.date.issued | 2016-12-12 | |
dc.identifier.citation | Cancer Cell, 2016, 30, (6), pp. 891-908 | |
dc.identifier.issn | 1535-6108 | |
dc.identifier.issn | 1878-3686 | |
dc.identifier.uri | http://hdl.handle.net/10453/159892 | |
dc.description.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. | |
dc.format | ||
dc.language | eng | |
dc.publisher | Elsevier BV | |
dc.relation.ispartof | Cancer Cell | |
dc.relation.isbasedon | 10.1016/j.ccell.2016.11.003 | |
dc.rights | info:eu-repo/semantics/closedAccess | |
dc.subject | 1109 Neurosciences, 1112 Oncology and Carcinogenesis | |
dc.subject.classification | Oncology & Carcinogenesis | |
dc.subject.mesh | Cell Line, Tumor | |
dc.subject.mesh | Cell Proliferation | |
dc.subject.mesh | Cell Survival | |
dc.subject.mesh | Central Nervous System Neoplasms | |
dc.subject.mesh | Chromatin | |
dc.subject.mesh | DNA Methylation | |
dc.subject.mesh | Dasatinib | |
dc.subject.mesh | Epigenesis, Genetic | |
dc.subject.mesh | Epigenomics | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Mutation | |
dc.subject.mesh | Protein Kinase Inhibitors | |
dc.subject.mesh | Pyrimidines | |
dc.subject.mesh | Receptor, Platelet-Derived Growth Factor beta | |
dc.subject.mesh | Rhabdoid Tumor | |
dc.subject.mesh | SMARCB1 Protein | |
dc.subject.mesh | Teratoma | |
dc.subject.mesh | Cell Line, Tumor | |
dc.subject.mesh | Chromatin | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Rhabdoid Tumor | |
dc.subject.mesh | Teratoma | |
dc.subject.mesh | Central Nervous System Neoplasms | |
dc.subject.mesh | Pyrimidines | |
dc.subject.mesh | Receptor, Platelet-Derived Growth Factor beta | |
dc.subject.mesh | Protein Kinase Inhibitors | |
dc.subject.mesh | Cell Proliferation | |
dc.subject.mesh | Cell Survival | |
dc.subject.mesh | DNA Methylation | |
dc.subject.mesh | Epigenesis, Genetic | |
dc.subject.mesh | Mutation | |
dc.subject.mesh | Epigenomics | |
dc.subject.mesh | Dasatinib | |
dc.subject.mesh | SMARCB1 Protein | |
dc.title | Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors. | |
dc.type | Journal Article | |
utslib.citation.volume | 30 | |
utslib.location.activity | United States | |
utslib.for | 1109 Neurosciences | |
utslib.for | 1112 Oncology and Carcinogenesis | |
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 | * |
dc.date.updated | 2022-08-11T00:55:46Z | |
pubs.issue | 6 | |
pubs.publication-status | Published | |
pubs.volume | 30 | |
utslib.citation.issue | 6 |
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.
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