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Cancer Cell. 2013 Dec 9;24(6):710-24. doi: 10.1016/j.ccr.2013.11.002.

Targeting oxidative stress in embryonal rhabdomyosarcoma.

Author information

1
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
2
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
3
Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
4
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
5
Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
6
Cytogenetics Shared Resource, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
7
Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
8
The Genome Institute, Washington University School of Medicine in St. Louis, St. Louis, MO 63108, USA.
9
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.
10
Division of Pediatric Hematology-Oncology, UT Southwestern Medical Center, Dallas, TX 75390, USA.
11
Division of Hematology-Oncology, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98105, USA.
12
Nationwide Children's Hospital, Columbus, OH 43205, USA.
13
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.
14
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.

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.

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PMID:
24332040
PMCID:
PMC3904731
DOI:
10.1016/j.ccr.2013.11.002
[Indexed for MEDLINE]
Free PMC Article
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