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

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 (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.

• Authors: Ruth T Casey, Mary A McLean, Benjamin G Challis, Terri P McVeigh, Anne Y Warren, Lee Mendil, Richard Houghton, Stefano De Sanctis, Vasilis Kosmoliaptsis, Richard N Sandford, Ferdia A Gallagher, Eamonn R Maher
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 2 Pg. 391-396 (01 15 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 31636096 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2019 American Association for Cancer Research.

Chemical References

• Fumarates
• SDHD protein, human
• Succinate Dehydrogenase
• Fumarate Hydratase

Topics

• Adult
• Female
• Fumarate Hydratase (genetics, metabolism)
• Fumarates (metabolism)
• Germ-Line Mutation
• Humans
• Kidney Neoplasms (diagnosis, metabolism)
• Leiomyomatosis (diagnosis, metabolism)
• Male
• Middle Aged
• Neoplastic Syndromes, Hereditary (diagnosis, metabolism)
• Proton Magnetic Resonance Spectroscopy (methods)
• Skin Neoplasms (diagnosis, metabolism)
• Succinate Dehydrogenase (genetics)
• Uterine Neoplasms (diagnosis, metabolism)