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James F Powers
James F Powers
Department of Pathology and Laboratory Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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Brent Cochran
Brent Cochran
Department of Developmental, Molecular and Chemical Biology
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James D Baleja
James D Baleja
Department of Developmental, Molecular and Chemical Biology
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Hadley D Sikes
Hadley D Sikes
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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Andrew D Pattison
Andrew D Pattison
Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria, Australia
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Xue Zhang
Xue Zhang
Department of Developmental, Molecular and Chemical Biology
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Inna Lomakin
Inna Lomakin
Department of Pathology and Laboratory Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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Annette Shepard-Barry
Annette Shepard-Barry
Department of Pathology and Laboratory Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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Karel Pacak
Karel Pacak
Section on Medical Neuroendocrinology, Eunice Kennedy Shriver Division National Institute of Child Health and Human Development, Bethesda, Maryland, USA
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Sun Jin Moon
Sun Jin Moon
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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Troy F Langford
Troy F Langford
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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Kassi Taylor Stein
Kassi Taylor Stein
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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Richard W Tothill
Richard W Tothill
Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria, Australia
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
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Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
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Yingbin Ouyang
Yingbin Ouyang
Cyagen US Inc, Santa Clara, California, USA
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Arthur S Tischler
Arthur S Tischler
Department of Pathology and Laboratory Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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Tumors caused by loss-of-function mutations in genes encoding TCA cycle enzymes have been recently discovered and are now of great interest. Mutations in succinate dehydrogenase (SDH) subunits cause pheochromocytoma/paraganglioma (PCPG) and syndromically associated tumors, which differ phenotypically and clinically from more common SDH-intact tumors of the same types. Consequences of SDH deficiency include rewired metabolism, pseudohypoxic signaling and altered redox balance. PCPG with SDHB mutations are particularly aggressive, and development of treatments has been hampered by lack of valid experimental models. Attempts to develop mouse models have been unsuccessful. Using a new strategy, we developed a xenograft and cell line model of SDH-deficient pheochromocytoma from rats with a heterozygous germline Sdhb mutation. The genome, transcriptome and metabolome of this model, called RS0, closely resemble those of SDHB-mutated human PCPGs, making it the most valid model now available. Strategies employed to develop RS0 may be broadly applicable to other SDH-deficient tumors.
James F Powers
James F Powers
Department of Pathology and Laboratory Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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Brent Cochran
Brent Cochran
Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, USA
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James D Baleja
James D Baleja
Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, USA
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Hadley D Sikes
Hadley D Sikes
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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Andrew D Pattison
Andrew D Pattison
Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria, Australia
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Xue Zhang
Xue Zhang
Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, Massachusetts, USA
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Inna Lomakin
Inna Lomakin
Department of Pathology and Laboratory Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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Annette Shepard-Barry
Annette Shepard-Barry
Department of Pathology and Laboratory Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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Karel Pacak
Karel Pacak
Section on Medical Neuroendocrinology, Eunice Kennedy Shriver Division National Institute of Child Health and Human Development, Bethesda, Maryland, USA
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Sun Jin Moon
Sun Jin Moon
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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Troy F Langford
Troy F Langford
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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Kassi Taylor Stein
Kassi Taylor Stein
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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Richard W Tothill
Richard W Tothill
Department of Clinical Pathology, University of Melbourne, Melbourne, Victoria, Australia
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
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Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
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Yingbin Ouyang
Yingbin Ouyang
Cyagen US Inc, Santa Clara, California, USA
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Arthur S Tischler
Arthur S Tischler
Department of Pathology and Laboratory Medicine, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
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