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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.
Afiliação
  • Torchia J; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G0A4, Canada; Department of Paediatrics, University of Toronto, Toronto, ON M5G0A4, Canada; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain
  • Golbourn B; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G0A4, Canada; Division of Neurosurgery, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Feng S; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G0A4, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G1L7, Canada.
  • Ho KC; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Sin-Chan P; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G0A4, Canada; Department of Paediatrics, University of Toronto, Toronto, ON M5G0A4, Canada; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain
  • Vasiljevic A; Department of Pathology, Groupement Hospitalier Est, CHU de Lyon, Lyon-Bron 69677, France.
  • Norman JD; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Guilhamon P; Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G1L7, Canada.
  • Garzia L; Program in Developmental & Stem Cell Biology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Agamez NR; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Lu M; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Chan TS; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G0A4, Canada; Department of Paediatrics, University of Toronto, Toronto, ON M5G0A4, Canada; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain
  • Picard D; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • de Antonellis P; Program in Developmental & Stem Cell Biology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Khuong-Quang DA; Department of Pediatrics, McGill University, Montreal, QC H3Z2Z3, Canada; Department of Human Genetics, McGill University, Montreal, QC H3Z2Z3, Canada.
  • Planello AC; Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G1L7, Canada.
  • Zeller C; Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G1L7, Canada.
  • Barsyte-Lovejoy D; Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G1L7, Canada.
  • Lafay-Cousin L; Division of Pediatric Hematology/Oncology, Alberta Children's Hospital, AB T3B6A8, Canada.
  • Letourneau L; Genome Quebec Innovation Centre, McGill University, Montreal, QC H3A1A4, Canada.
  • Bourgey M; Genome Quebec Innovation Centre, McGill University, Montreal, QC H3A1A4, Canada.
  • Yu M; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Gendoo DMA; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Dzamba M; Department of Computer Science, University of Toronto, Toronto, ON M5G0A4, Canada.
  • Barszczyk M; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Medina T; Princess Margaret Cancer Center, University Health Network, Toronto, ON M5G1L7, Canada.
  • Riemenschneider AN; Division of Neurosurgery, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Morrissy AS; Program in Developmental & Stem Cell Biology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Ra YS; Department of Neurosurgery, Asan Medical Center, Seoul 138-736, Korea.
  • Ramaswamy V; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Remke M; Division of Hematology/Oncology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Dunham CP; Division of Anatomic Pathology, Children's and Women's Health Centre of B.C, University of British Columbia, Vancouver, BC V6H3N1, Canada.
  • Yip S; Department of Pathology & Laboratory Medicine, University of British Columbia, V6T1Z3, Canada.
  • Ng HK; Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Hong Kong, China.
  • Lu JQ; Laboratory Medicine and Pathology, Stollery Children's Hospital, University of Alberta, Edmonton, AB T2W3N2, Canada.
  • Mehta V; Division of Neurosurgery, Stollery Children's Hospital, University of Alberta, Edmonton, AB T2W3N2, Canada.
  • Albrecht S; Department of Pathology, McGill University, Montreal, QC H3Z2Z3, Canada.
  • Pimentel J; Divison of Pathology, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon 1649-035, Portugal.
  • Chan JA; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB T2N1N4, Canada.
  • Somers GR; Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
  • Faria CC; Department of Neurosurgery, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon 1649-035, Portugal.
  • Roque L; Cytometry and Cytogenetic Laboratory, CIPM, Portuguese Cancer Institute, Lisbon 1099-023, Portugal.
  • Fouladi M; Division of Oncology, Department of Cancer and Blood Diseases, Cincinnati Children's Hospital, Cincinnati, OH 45229, USA.
  • Hoffman LM; Department of Pediatrics, University of Colorado, Denver, CO 80045, USA.
  • Moore AS; Oncology Service, Children's Health Queensland Hospital; University of Queensland Diamantina Institute, Brisbane, QLD 4102, Australia.
  • Wang Y; Research Institute of Health Development Strategies, Fudan University, Shanghai 200032, China.
  • Choi SA; Division of Pediatric Neurosurgery, Seoul National University Children's Hospital, Seoul 03080, Korea.
  • Hansford JR; Royal Children's Hospital, Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia.
  • Catchpoole D; Children's Cancer Research Unit, Children's Hospital at Westmead, Westmead, NSW 2145, Australia.
  • Birks DK; Department of Pediatrics, University of Colorado, Denver, CO 80045, USA.
Cancer Cell ; 30(6): 891-908, 2016 Dec 12.
Article em En | MEDLINE | ID: mdl-27960086
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Teratoma / Cromatina / Neoplasias do Sistema Nervoso Central / Tumor Rabdoide / Receptor beta de Fator de Crescimento Derivado de Plaquetas / Epigenômica / Proteína SMARCB1 Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cancer Cell Ano de publicação: 2016 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Teratoma / Cromatina / Neoplasias do Sistema Nervoso Central / Tumor Rabdoide / Receptor beta de Fator de Crescimento Derivado de Plaquetas / Epigenômica / Proteína SMARCB1 Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Cancer Cell Ano de publicação: 2016 Tipo de documento: Article