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Identification of Therapeutic Targets in Rhabdomyosarcoma through Integrated Genomic, Epigenomic, and Proteomic Analyses.
Stewart, Elizabeth; McEvoy, Justina; Wang, Hong; Chen, Xiang; Honnell, Victoria; Ocarz, Monica; Gordon, Brittney; Dapper, Jason; Blankenship, Kaley; Yang, Yanling; Li, Yuxin; Shaw, Timothy I; Cho, Ji-Hoon; Wang, Xusheng; Xu, Beisi; Gupta, Pankaj; Fan, Yiping; Liu, Yu; Rusch, Michael; Griffiths, Lyra; Jeon, Jongrye; Freeman, Burgess B; Clay, Michael R; Pappo, Alberto; Easton, John; Shurtleff, Sheila; Shelat, Anang; Zhou, Xin; Boggs, Kristy; Mulder, Heather; Yergeau, Donald; Bahrami, Armita; Mardis, Elaine R; Wilson, Richard K; Zhang, Jinghui; Peng, Junmin; Downing, James R; Dyer, Michael A.
Afiliação
  • Stewart E; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105-3678, USA; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • McEvoy J; Departments of Molecular and Cellular Biology and Pediatrics, BIO5 Institute, University of Arizona, Tucson, AZ 85721, USA.
  • Wang H; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Integrated Biomedical Sciences, University of Tennessee Health Science Center, Memphis, TN 38105, USA.
  • Chen X; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Honnell V; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105-3678, USA; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Ocarz M; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105-3678, USA.
  • Gordon B; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105-3678, USA.
  • Dapper J; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105-3678, USA; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Blankenship K; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Yang Y; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Li Y; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Proteomics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Shaw TI; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Proteomics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Cho JH; Proteomics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Wang X; Proteomics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Xu B; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Gupta P; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Fan Y; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Liu Y; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Rusch M; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Griffiths L; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105-3678, USA.
  • Jeon J; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105-3678, USA.
  • Freeman BB; Preclinical Pharmacokinetics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Clay MR; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Pappo A; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Easton J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Shurtleff S; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Shelat A; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Zhou X; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Boggs K; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Mulder H; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Yergeau D; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Bahrami A; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Mardis ER; The McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA; Department of Genetics, Washington University, St. Louis, MO 63108, USA; Department of Medicine, Washington University, St. Louis, MO 63108, USA.
  • Wilson RK; The McDonnell Genome Institute, Washington University, St. Louis, MO 63108, USA; Department of Genetics, Washington University, St. Louis, MO 63108, USA; Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA.
  • Zhang J; Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Peng J; Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Downing JR; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  • Dyer MA; Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MS 323, Memphis, TN 38105-3678, USA; Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, TN 38105, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, US
Cancer Cell ; 34(3): 411-426.e19, 2018 09 10.
Article em En | MEDLINE | ID: mdl-30146332
Personalized cancer therapy targeting somatic mutations in patient tumors is increasingly being incorporated into practice. Other therapeutic vulnerabilities resulting from changes in gene expression due to tumor specific epigenetic perturbations are progressively being recognized. These genomic and epigenomic changes are ultimately manifest in the tumor proteome and phosphoproteome. We integrated transcriptomic, epigenomic, and proteomic/phosphoproteomic data to elucidate the cellular origins and therapeutic vulnerabilities of rhabdomyosarcoma (RMS). We discovered that alveolar RMS occurs further along the developmental program than embryonal RMS. We also identified deregulation of the RAS/MEK/ERK/CDK4/6, G2/M, and unfolded protein response pathways through our integrated analysis. Comprehensive preclinical testing revealed that targeting the WEE1 kinase in the G2/M pathway is the most effective approach in vivo for high-risk RMS.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Rabdomiossarcoma / Proteínas Tirosina Quinases / Proteínas Nucleares / Biomarcadores Tumorais / Proteínas de Ciclo Celular / Neoplasias Musculares / Antineoplásicos Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Rabdomiossarcoma / Proteínas Tirosina Quinases / Proteínas Nucleares / Biomarcadores Tumorais / Proteínas de Ciclo Celular / Neoplasias Musculares / Antineoplásicos Idioma: En Ano de publicação: 2018 Tipo de documento: Article