title: Targeting oxidative stress in embryonal rhabdomyosarcoma.
abstract: Rhabdomyosarcoma is a soft-tissue sarcoma with molecular and cellular features of developing skeletal muscle. Rhabdomyosarcoma has two major histologic subtypes, embryonal and alveolar, each with distinct clinical, molecular, and genetic features. Genomic analysis shows that embryonal tumors have more structural and copy number variations than alveolar tumors. Mutations in the RAS/NF1 pathway are significantly associated with intermediate- and high-risk embryonal rhabdomyosarcomas (ERMS). In contrast, alveolar rhabdomyosarcomas (ARMS) have fewer genetic lesions overall and no known recurrently mutated cancer consensus genes. To identify therapeutics for ERMS, we developed and characterized orthotopic xenografts of tumors that were sequenced in our study. High-throughput screening of primary cultures derived from those xenografts identified oxidative stress as a pathway of therapeutic relevance for ERMS.
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Xiang
authors: X
authors: Chen
authors: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Elizabeth
authors: E
authors: Stewart
authors: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Anang A
authors: AA
authors: Shelat
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Chunxu
authors: C
authors: Qu
authors: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Armita
authors: A
authors: Bahrami
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Mark
authors: M
authors: Hatley
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Gang
authors: G
authors: Wu
authors: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Cori
authors: C
authors: Bradley
authors: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Justina
authors: J
authors: McEvoy
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Alberto
authors: A
authors: Pappo
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Sheri
authors: S
authors: Spunt
authors: Cytogenetics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Marcus B
authors: MB
authors: Valentine
authors: Cytogenetics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Virginia
authors: V
authors: Valentine
authors: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Fred
authors: F
authors: Krafcik
authors: Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Walter H
authors: WH
authors: Lang
authors: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Monika
authors: M
authors: Wierdl
authors: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Lyudmila
authors: L
authors: Tsurkan
authors: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Viktor
authors: V
authors: Tolleman
authors: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Sara M
authors: SM
authors: Federico
authors: Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Chris
authors: C
authors: Morton
authors: The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA.
authors: Charles
authors: C
authors: Lu
authors: The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA; Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA; Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA; Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA.
authors: Li
authors: L
authors: Ding
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: John
authors: J
authors: Easton
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Michael
authors: M
authors: Rusch
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Panduka
authors: P
authors: Nagahawatte
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Jianmin
authors: J
authors: Wang
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Matthew
authors: M
authors: Parker
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Lei
authors: L
authors: Wei
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Erin
authors: E
authors: Hedlund
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: David
authors: D
authors: Finkelstein
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Michael
authors: M
authors: Edmonson
authors: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Sheila
authors: S
authors: Shurtleff
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Kristy
authors: K
authors: Boggs
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Heather
authors: H
authors: Mulder
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Donald
authors: D
authors: Yergeau
authors: Division of Pediatric Hematology-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors: Steve
authors: S
authors: Skapek
authors: Division of Hematology-Oncology, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98105, USA.
authors: Douglas S
authors: DS
authors: Hawkins
authors: Nationwide Children's Hospital, Columbus, OH 43205, USA.
authors: Nilsa
authors: N
authors: Ramirez
authors: Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Philip M
authors: PM
authors: Potter
authors: Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: John A
authors: JA
authors: Sandoval
authors: Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Andrew M
authors: AM
authors: Davidoff
authors: The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA; Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA; Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA.
authors: Elaine R
authors: ER
authors: Mardis
authors: The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA; Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA; Siteman Cancer Center, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA.
authors: Richard K
authors: RK
authors: Wilson
authors: Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Jinghui
authors: J
authors: Zhang
authors: Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: James R
authors: JR
authors: Downing
authors: Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: michael.dyer@stjude.org.
authors: Michael A
authors: MA
authors: Dyer
mesh_terms: D000818:Animals; D060965:Clonal Evolution; D018628:Gene Dosage; D006706:Homeostasis; D006801:Humans; D019656:Loss of Heterozygosity; D051379:Mice; D009154:Mutation; D018384:Oxidative Stress; D018233:Rhabdomyosarcoma, Embryonal / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism