RT Casey, MA McLean, BG Challis, TP McVeigh, AY Warren, L Mendil, R Houghton, S De Sanctis, V Kosmoliaptsis, RN Sandford, FA Gallagher, ER Maher
Clin Cancer Res
PURPOSE: Inherited pathogenic variants in genes encoding the metabolic enzymes succinate dehydrogenase (SDH) and fumarate hydratase (FH) predispose to tumour development through accumulation of oncometabolites (succinate and fumarate respectively) (1). Non-invasive in vivo detection of tumour succinate by proton magnetic resonance spectroscopy (1H-MRS) has been reported in SDH-deficient tumours 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 tumour immunohistochemistry when available. RESULTS: Here, we have demonstrated a proof-of-principle that 1H-MRS can provide a non-invasive diagnosis of hereditary leiomyomatosis and renal cell cancer syndrome or Reed syndrome through detection of fumarate accumulation in vivo. Conclusion: This study demonstrates that in vivo detection of fumarate could be employed as a functional biomarker.