1. Fumarate Metabolic Signature for the Detection of Reed Syndrome in Humans.
- Author
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Casey RT, McLean MA, Challis BG, McVeigh TP, Warren AY, Mendil L, Houghton R, De Sanctis S, Kosmoliaptsis V, Sandford RN, Gallagher FA, and Maher ER
- Subjects
- Adult, Female, Fumarate Hydratase genetics, Fumarate Hydratase metabolism, Humans, Kidney Neoplasms metabolism, Leiomyomatosis metabolism, Male, Middle Aged, Neoplastic Syndromes, Hereditary metabolism, Skin Neoplasms metabolism, Succinate Dehydrogenase genetics, Uterine Neoplasms metabolism, Fumarates metabolism, Germ-Line Mutation, Kidney Neoplasms diagnosis, Leiomyomatosis diagnosis, Neoplastic Syndromes, Hereditary diagnosis, Proton Magnetic Resonance Spectroscopy methods, Skin Neoplasms diagnosis, Uterine Neoplasms diagnosis
- Abstract
Purpose: Inherited pathogenic variants in genes encoding the metabolic enzymes succinate dehydrogenase (SDH) and fumarate hydratase predispose to tumor development through accumulation of oncometabolites (succinate and fumarate, respectively; ref. 1). Noninvasive in vivo detection of tumor succinate by proton magnetic resonance spectroscopy (
1 H-MRS) has been reported in SDH-deficient tumors, but the potential utility of this approach in the management of patients with hereditary leiomyomatosis and renal cell cancer syndrome or Reed syndrome is unknown., Experimental Design: Magnetic resonance spectroscopy (1 H-MRS) was performed on three cases and correlated with germline genetic results and tumor IHC when available., Results: Here, we have demonstrated a proof of principle that1 H-MRS can provide a noninvasive diagnosis of hereditary leiomyomatosis and renal cell cancer syndrome or Reed syndrome through detection of fumarate accumulation in vivo ., Conclusions: This study demonstrates that in vivo detection of fumarate could be employed as a functional biomarker., (©2019 American Association for Cancer Research.)- Published
- 2020
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