Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma

Xiang Chen; Elizabeth Stewart; AnangA Shelat; Chunxu Qu; Armita Bahrami; Mark Hatley; Gang Wu; Cori Bradley; Justina McEvoy; Alberto Pappo; Sheri Spunt; MarcusB Valentine; Virginia Valentine; Fred Krafcik; WalterH Lang; Monika Wierdl; Lyudmila Tsurkan; Viktor Tolleman; SaraM Federico; Chris Morton; Charles Lu; Li Ding; John Easton; Michael Rusch; Panduka Nagahawatte; Jianmin Wang; Matthew Parker; Lei Wei; Erin Hedlund; David Finkelstein; Michael Edmonson; Sheila Shurtleff; Kristy Boggs; Heather Mulder; Donald Yergeau; Steve Skapek; DouglasS Hawkins; Nilsa Ramirez; PhilipM Potter; JohnA Sandoval; AndrewM Davidoff; ElaineR Mardis; RichardK Wilson; Jinghui Zhang; JamesR Downing; MichaelA Dyer

doi:10.1016/j.ccr.2013.11.002

Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma

Xiang Chen, Elizabeth Stewart, AnangA Shelat, Chunxu Qu, Armita Bahrami, Mark Hatley, Gang Wu, Cori Bradley, Justina McEvoy, Alberto Pappo, Sheri Spunt, MarcusB Valentine, Virginia Valentine, Fred Krafcik, WalterH Lang, Monika Wierdl, Lyudmila Tsurkan, Viktor Tolleman, SaraM Federico, Chris MortonCharles Lu, Li Ding, John Easton, Michael Rusch, Panduka Nagahawatte, Jianmin Wang, Matthew Parker, Lei Wei, Erin Hedlund, David Finkelstein, Michael Edmonson, Sheila Shurtleff, Kristy Boggs, Heather Mulder, Donald Yergeau, Steve Skapek, DouglasS Hawkins, Nilsa Ramirez, PhilipM Potter, JohnA Sandoval, AndrewM Davidoff, ElaineR Mardis, RichardK Wilson, Jinghui Zhang, JamesR Downing, MichaelA Dyer

Research output: Contribution to journal › Article › peer-review

234 Scopus citations

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.

Original language	English (US)
Pages (from-to)	710-724
Number of pages	15
Journal	Cancer Cell
Volume	24
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2013.11.002
State	Published - Dec 9 2013

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.ccr.2013.11.002

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Chen, X., Stewart, E., Shelat, A., Qu, C., Bahrami, A., Hatley, M., Wu, G., Bradley, C., McEvoy, J., Pappo, A., Spunt, S., Valentine, M., Valentine, V., Krafcik, F., Lang, W., Wierdl, M., Tsurkan, L., Tolleman, V., Federico, S., ... Dyer, M. (2013). Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma. Cancer Cell, 24(6), 710-724. https://doi.org/10.1016/j.ccr.2013.11.002

Chen, X, Stewart, E, Shelat, A, Qu, C, Bahrami, A, Hatley, M, Wu, G, Bradley, C, McEvoy, J, Pappo, A, Spunt, S, Valentine, M, Valentine, V, Krafcik, F, Lang, W, Wierdl, M, Tsurkan, L, Tolleman, V, Federico, S, Morton, C, Lu, C, Ding, L, Easton, J, Rusch, M, Nagahawatte, P, Wang, J, Parker, M, Wei, L, Hedlund, E, Finkelstein, D, Edmonson, M, Shurtleff, S, Boggs, K, Mulder, H, Yergeau, D, Skapek, S, Hawkins, D, Ramirez, N, Potter, P, Sandoval, J, Davidoff, A, Mardis, E, Wilson, R, Zhang, J, Downing, J & Dyer, M 2013, 'Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma', Cancer Cell, vol. 24, no. 6, pp. 710-724. https://doi.org/10.1016/j.ccr.2013.11.002

@article{ce71dbe7a8bc4f7d83e63f40c842f688,

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.",

author = "Xiang Chen and Elizabeth Stewart and AnangA Shelat and Chunxu Qu and Armita Bahrami and Mark Hatley and Gang Wu and Cori Bradley and Justina McEvoy and Alberto Pappo and Sheri Spunt and MarcusB Valentine and Virginia Valentine and Fred Krafcik and WalterH Lang and Monika Wierdl and Lyudmila Tsurkan and Viktor Tolleman and SaraM Federico and Chris Morton and Charles Lu and Li Ding and John Easton and Michael Rusch and Panduka Nagahawatte and Jianmin Wang and Matthew Parker and Lei Wei and Erin Hedlund and David Finkelstein and Michael Edmonson and Sheila Shurtleff and Kristy Boggs and Heather Mulder and Donald Yergeau and Steve Skapek and DouglasS Hawkins and Nilsa Ramirez and PhilipM Potter and JohnA Sandoval and AndrewM Davidoff and ElaineR Mardis and RichardK Wilson and Jinghui Zhang and JamesR Downing and MichaelA Dyer",

note = "Funding Information: We thank S. Frase for assistance with electron microscopy, B. Vadodaria for technical assistance, and A. McArthur for editing the manuscript. This work was supported, in part, by a Cancer Center Support grant (CA21765) from the National Cancer Institute, National Institutes of Health grants (EY014867, EY018599, and CA168875) to M.A.D., and the American Lebanese Syrian Associated Charities. M.A.D. is a Howard Hughes Medical Institute Investigator. The WGS was supported as part of the SJCRH–Washington University Pediatric Cancer Genome Project. Finally, we thank John and Andra Tully and the Tully Family Foundation for generous support of Pediatric Solid Tumor Research at SJCRH. ",

year = "2013",

month = dec,

day = "9",

doi = "10.1016/j.ccr.2013.11.002",

language = "English (US)",

volume = "24",

pages = "710--724",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

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T1 - Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma

AU - Chen, Xiang

AU - Stewart, Elizabeth

AU - Shelat, AnangA

AU - Qu, Chunxu

AU - Bahrami, Armita

AU - Hatley, Mark

AU - Wu, Gang

AU - Bradley, Cori

AU - McEvoy, Justina

AU - Pappo, Alberto

AU - Spunt, Sheri

AU - Valentine, MarcusB

AU - Valentine, Virginia

AU - Krafcik, Fred

AU - Lang, WalterH

AU - Wierdl, Monika

AU - Tsurkan, Lyudmila

AU - Tolleman, Viktor

AU - Federico, SaraM

AU - Morton, Chris

AU - Lu, Charles

AU - Ding, Li

AU - Easton, John

AU - Rusch, Michael

AU - Nagahawatte, Panduka

AU - Wang, Jianmin

AU - Parker, Matthew

AU - Wei, Lei

AU - Hedlund, Erin

AU - Finkelstein, David

AU - Edmonson, Michael

AU - Shurtleff, Sheila

AU - Boggs, Kristy

AU - Mulder, Heather

AU - Yergeau, Donald

AU - Skapek, Steve

AU - Hawkins, DouglasS

AU - Ramirez, Nilsa

AU - Potter, PhilipM

AU - Sandoval, JohnA

AU - Davidoff, AndrewM

AU - Mardis, ElaineR

AU - Wilson, RichardK

AU - Zhang, Jinghui

AU - Downing, JamesR

AU - Dyer, MichaelA

N1 - Funding Information: We thank S. Frase for assistance with electron microscopy, B. Vadodaria for technical assistance, and A. McArthur for editing the manuscript. This work was supported, in part, by a Cancer Center Support grant (CA21765) from the National Cancer Institute, National Institutes of Health grants (EY014867, EY018599, and CA168875) to M.A.D., and the American Lebanese Syrian Associated Charities. M.A.D. is a Howard Hughes Medical Institute Investigator. The WGS was supported as part of the SJCRH–Washington University Pediatric Cancer Genome Project. Finally, we thank John and Andra Tully and the Tully Family Foundation for generous support of Pediatric Solid Tumor Research at SJCRH.

PY - 2013/12/9

Y1 - 2013/12/9

N2 - 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.

AB - 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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SP - 710

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JO - Cancer Cell

JF - Cancer Cell

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ER -

Targeting Oxidative Stress in Embryonal Rhabdomyosarcoma

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