Integrated (epi)-Genomic Analyses Identify Subgroup-Specific Therapeutic Targets in CNS Rhabdoid Tumors

被引：195

作者：

Torchia, Jonathon ^{[1
,2
,7
,13
]}

Golbourn, Brian ^{[1
,8
,13
]}

Feng, Shengrui ^{[3
,14
]}

Ho, King Ching ^{[7
,13
]}

Sin-Chan, Patrick ^{[1
,2
,7
,13
]}

Vasiljevic, Alexandre ^{[15
]}

Norman, Joseph D. ^{[7
,13
]}

Guilhamon, Paul ^{[14
]}

Garzia, Livia ^{[10
,13
]}

Agamez, Natalia R. ^{[7
,13
]}

Lu, Mei ^{[7
,13
]}

Chan, Tiffany S. ^{[1
,2
,7
,13
]}

Picard, Daniel ^{[7
,13
]}

de Antonellis, Pasqualino ^{[10
,13
]}

Khuong-Quang, Dong-Anh ^{[16
,17
]}

Planello, Aline C. ^{[14
]}

Zeller, Constanze ^{[14
]}

Barsyte-Lovejoy, Dalia ^{[14
]}

Lafay-Cousin, Lucie ^{[20
]}

Letourneau, Louis ^{[19
]}

Bourgey, Mathieu ^{[19
]}

Yu, Man ^{[13
]}

Gendoo, Deena M. A. ^{[7
,13
]}

Dzamba, Misko ^{[5
]}

Barszczyk, Mark ^{[13
]}

Medina, Tiago ^{[14
]}

Riemenschneider, Alexandra N. ^{[8
,13
]}

Morrissy, A. Sorana ^{[10
,13
]}

Ra, Young-Shin ^{[22
]}

Ramaswamy, Vijay ^{[7
,13
]}

Remke, Marc ^{[7
,13
]}

Dunham, Christopher P. ^{[23
]}

Yip, Stephen ^{[25
]}

Ng, Ho-keung ^{[26
]}

Lu, Jian-Qiang ^{[27
]}

Mehta, Vivek ^{[28
]}

Albrecht, Steffen ^{[18
]}

Pimentel, Jose ^{[30
]}

Chan, Jennifer A. ^{[21
]}

Somers, Gino R. ^{[12
]}

Faria, Claudia C. ^{[31
]}

Roque, Lucia ^{[32
]}

Fouladi, Maryam ^{[33
]}

Hoffman, Lindsey M. ^{[34
]}

Moore, Andrew S. ^{[35
]}

Wang, Yin ^{[36
]}

Choi, Seung Ah ^{[37
]}

Hansford, Jordan R. ^{[38
]}

Catchpoole, Daniel ^{[39
]}

Birks, Diane K. ^{[34
]}

机构：

[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G0A4, Canada

[2] Univ Toronto, Dept Paediat, Toronto, ON M5G0A4, Canada

[3] Univ Toronto, Dept Med Biophys, Toronto, ON M5G0A4, Canada

[4] Univ Toronto, Dept Mol Genet, Toronto, ON M5G0A4, Canada

[5] Univ Toronto, Dept Comp Sci, Toronto, ON M5G0A4, Canada

[6] Univ Toronto, Dept Surg, Toronto, ON M5G0A4, Canada

[7] Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada

[8] Hosp Sick Children, Div Neurosurg, Toronto, ON M5G 1X8, Canada

[9] Hosp Sick Children, Div Pathol, Toronto, ON M5G 1X8, Canada

[10] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada

[11] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON M5G 1X8, Canada

[12] Hosp Sick Children, Dept Paediat Lab Med, Toronto, ON M5G 1X8, Canada

[13] Hosp Sick Children, Arthur & Sonia Labatt Brain Tumour Res Ctr, Toronto, ON M5G 1X8, Canada

[14] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada

[15] CHU Lyon, Grp Hosp Est, Dept Pathol, F-69677 Lyon, France

[16] McGill Univ, Dept Pediat, Montreal, PQ H3Z2Z3, Canada

[17] McGill Univ, Dept Human Genet, Montreal, PQ H3Z2Z3, Canada

[18] McGill Univ, Dept Pathol, Montreal, PQ H3Z2Z3, Canada

[19] McGill Univ, Genome Quebec Innovat Ctr, Montreal, PQ H3A1A4, Canada

[20] Alberta Childrens Prov Gen Hosp, Div Pediat Hematol Oncol, Edmonton, AB T3B6A8, Canada

[21] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB T2N 1N4, Canada

[22] Asan Med Ctr, Dept Neurosurg, Seoul 138736, South Korea

[23] Univ British Columbia, Childrens & Womens Hlth Ctr BC, Div Anat Pathol, Vancouver, BC V6H3N1, Canada

[24] Univ British Columbia, Childrens & Womens Hlth Ctr BC, Div Hematol & Oncol, Vancouver, BC V6H3N1, Canada

[25] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V6T 1Z3, Canada

[26] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Hong Kong, Hong Kong, Peoples R China

[27] Univ Alberta, Stollery Childrens Hosp, Lab Med & Pathol, Edmonton, AB T2W3N2, Canada

[28] Univ Alberta, Stollery Childrens Hosp, Div Neurosurg, Edmonton, AB T2W3N2, Canada

[29] Univ Alberta, Stollery Childrens Hosp, Div Pediat Hematol Oncol, Edmonton, AB T2W3N2, Canada

[30] Ctr Hosp Lisboa Norte, Hosp Santa Maria, Div Pathol, P-1649035 Lisbon, Portugal

[31] Ctr Hosp Lisboa Norte, Hosp Santa Maria, Dept Neurosurg, P-1649035 Lisbon, Portugal

[32] Portuguese Canc Inst, CIPM, Cytometry & Cytogenet Lab, P-1099023 Lisbon, Portugal

[33] Cincinnati Childrens Hosp, Div Oncol, Dept Canc & Blood Dis, Cincinnati, OH 45229 USA

[34] Univ Colorado, Dept Pediat, Denver, CO 80045 USA

[35] Univ Queensland, Diamantina Inst, Childrens Hlth Queensland Hosp, Oncol Serv, Brisbane, Qld 4102, Australia

[36] Fudan Univ, Res Inst Hlth Dev Strategies, Shanghai 200032, Peoples R China

[37] Seoul Natl Univ, Childrens Hosp, Div Pediat Neurosurg, Seoul 03080, South Korea

[38] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia

[39] Childrens Hosp Westmead, Childrens Canc Res Unit, Westmead, NSW 2145, Australia

[40] Univ Debrecen, Dept Neurosurg, H-4032 Debrecen, Hungary

[41] Semmelweis Univ, Dept Pediat 2, H-1094 Budapest, Hungary

[42] Univ Szeged, Dept Histopathol, H-6720 Szeged, Hungary

[43] Univ Montreal, CHU St Justine, Dept Pediat, Div Hematol Oncol, Montreal, PQ H3T 1C5, Canada

[44] Virginia Commonwealth Univ, Dept Neurosurg, Med Coll Virginia Campus, Richmond, VA 23298 USA

[45] Childrens Natl Med Ctr, Dept Oncol, Washington, DC 20010 USA

[46] St Jude Childrens Res Hosp, Div Neurooncol, 332 N Lauderdale St, Memphis, TN 38105 USA

[47] Taipei Vet Gen Hosp, Dept Med Res, Taipei 112, Taiwan

[48] Natl Yang Ming Univ, Taipei 112, Taiwan

[49] Kumamoto Univ, Dept Neurosurg, Kumamoto 8608556, Japan

[50] Childrens Med Ctr Israel, Dept Pediat Hematol Oncol, IL-49202 Petah Tiqwa, Israel

来源：

CANCER CELL | 2016年 / 30卷 / 06期

关键词：

ATYPICAL TERATOID/RHABDOID TUMORS; CHILDREN; GENE; EXPRESSION; MUTATIONS; CHROMATIN; DIFFERENTIATION; HSNF5/INI1; FOREBRAIN; DASATINIB;

D O I：

10.1016/j.ccell.2016.11.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：891 / 908

页数：18

共 42 条

[1] Radial glia serve as neuronal progenitors in all regions of the central nervous system [J].

Anthony, TE ;

Klein, C ;

Fishell, G ;

Heintz, N .

NEURON, 2004, 41 (06) :881-890

[2] Dasatinib: A potent SRC inhibitor in clinical development for the treatment of solid tumors [J].

Araujo, John ;

Logothetis, Christopher .

CANCER TREATMENT REVIEWS, 2010, 36 (06) :492-500

[3] High expression of BMP pathway genes distinguishes a subset of atypical teratoid/rhabdoid tumors associated with shorter survival [J].

Birks, Diane K. ;

Donson, Andrew M. ;

Patel, Purvi R. ;

Dunham, Christopher ;

Muscat, Andrea ;

Algar, Elizabeth M. ;

Ashley, David M. ;

Kleinschmidt-DeMasters, B. K. ;

Vibhakar, Rajeev ;

Handler, Michael H. ;

Foreman, Nicholas K. .

NEURO-ONCOLOGY, 2011, 13 (12) :1296-1307

[4] Frequent hSNF5/INI1 Germline Mutations in Patients with Rhabdoid Tumor [J].

Bourdeaut, Franck ;

Lequin, Delphine ;

Brugieres, Laurence ;

Reynaud, Stephanie ;

Dufour, Christelle ;

Doz, Francois ;

Andre, Nicolas ;

Stephan, Jean-Louis ;

Perel, Yves ;

Oberlin, Odile ;

Orbach, Daniel ;

Bergeron, Christophe ;

Rialland, Xavier ;

Freneaux, Paul ;

Ranchere, Dominique ;

Figarella-Branger, Dominique ;

Audry, Georges ;

Puget, Stephanie ;

Evans, D. Gareth ;

Ferreres Pinas, Joan Carles ;

Capra, Valeria ;

Mosseri, Veronique ;

Coupier, Isabelle ;

Gauthier-Villars, Marion ;

Pierron, Gaelle ;

Delattre, Olivier .

CLINICAL CANCER RESEARCH, 2011, 17 (01) :31-38

[5]

Cecconi F, 1997, DEV DYNAM, V210, P184, DOI 10.1002/(SICI)1097-0177(199710)210:2<184::AID-AJA10>3.0.CO

[6]

2-E

[7] Intensive Multimodality Treatment for Children With Newly Diagnosed CNS Atypical Teratoid Rhabdoid Tumor [J].

Chi, Susan N. ;

Zimmerman, Mary Ann ;

Yao, Xiaopan ;

Cohen, Kenneth J. ;

Burger, Peter ;

Biegel, Jaclyn A. ;

Rorke-Adams, Lucy B. ;

Fisher, Michael J. ;

Janss, Anna ;

Mazewski, Claire ;

Goldman, Stewart ;

Manley, Peter E. ;

Bowers, Daniel C. ;

Bendel, Anne ;

Rubin, Joshua ;

Turner, Christopher D. ;

Marcus, Karen J. ;

Goumnerova, Liliana ;

Ullrich, Nicole J. ;

Kieran, Mark W. .

JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (03) :385-389

[8] Genome-Wide Profiles of Extra-cranial Malignant Rhabdoid Tumors Reveal Heterogeneity and Dysregulated Developmental Pathways [J].

Chun, Hye-Jung E. ;

Lim, Emilia L. ;

Heravi-Moussavi, Alireza ;

Saberi, Saeed ;

Mungall, Karen L. ;

Bilenky, Mikhail ;

Carles, Annaick ;

Tse, Kane ;

Shlafman, Inna ;

Zhu, Kelsey ;

Qian, Jenny Q. ;

Palmquist, Diana L. ;

He, An ;

Long, William ;

Goya, Rodrigo ;

Ng, Michelle ;

LeBlanc, Veronique G. ;

Pleasance, Erin ;

Thiessen, Nina ;

Wong, Tina ;

Chuah, Eric ;

Zhao, Yong-Jun ;

Schein, Jacquie E. ;

Gerhard, Daniela S. ;

Taylor, Michael D. ;

Mungall, Andrew J. ;

Moore, Richard A. ;

Ma, Yussanne ;

Jones, Steven J. M. ;

Perlman, Elizabeth J. ;

Hirst, Martin ;

Marra, Marco A. .

CANCER CELL, 2016, 29 (03) :394-406

[9] Spectrum of SMARCB1/INI1 Mutations in Familial and Sporadic Rhabdoid Tumors [J].

Eaton, Katherine W. ;

Tooke, Laura S. ;

Wainwright, Luanne M. ;

Judkins, Alexander R. ;

Biegel, Jaclyn A. .

PEDIATRIC BLOOD & CANCER, 2011, 56 (01) :7-15

[10]

Ericson J, 1998, DEVELOPMENT, V125, P1005

← 1 2 3 4 5 →