Fumarate Metabolic Signature for the Detection of Reed Syndrome in Humans.

Casey, Ruth T; McLean, Mary A; Challis, Benjamin G; McVeigh, Terri P; Warren, Anne Y; Mendil, Lee; Houghton, Richard; De Sanctis, Stefano et al. · Clin Cancer Res · 2020

case_series · Level IV

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Abstract

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 <i>in vivo</i> detection of tumor succinate by proton magnetic resonance spectroscopy (<sup>1</sup>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. Magnetic resonance spectroscopy (<sup>1</sup>H-MRS) was performed on three cases and correlated with germline genetic results and tumor IHC when available. Here, we have demonstrated a proof of principle that <sup>1</sup>H-MRS can provide a noninvasive diagnosis of hereditary leiomyomatosis and renal cell cancer syndrome or Reed syndrome through detection of fumarate accumulation <i>in vivo</i>. This study demonstrates that <i>in vivo</i> detection of fumarate could be employed as a functional biomarker.

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