Fumarate Metabolic Signature for the Detection of Reed Syndrome in Humans
Ruth T Casey1,2, Mary A McLean3, Benjamin G Challis2
1Department of Medical Genetics, University of Cambridge and NIHR Cambridge Biomedical Research Centre and Cancer Research UK Cambridge Centre, Cambridge, United Kingdom. rc674@medschl.cam.ac.uk.
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 (1H-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 (1H-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 that 1H-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.
More Related Videos
09:16Real-Time Analysis of Bioenergetics in Primary Human Retinal Pigment Epithelial Cells Using High-Resolution Respirometry
Published on: February 3, 2023
09:40Phosphorus-31 Magnetic Resonance Spectroscopy: A Tool for Measuring In Vivo Mitochondrial Oxidative Phosphorylation Capacity in Human Skeletal Muscle
Published on: January 19, 2017