Fumarate Metabolic Signature for the Detection of Reed Syndrome in Humans

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

doi:10.1158/1078-0432.CCR-19-1729

Fumarate Metabolic Signature for the Detection of Reed Syndrome in Humans

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

University of Cambridge and NIHR Cambridge Biomedical Research Centre and Cancer Research UK Cambridge Centre and Cambridge University Hospitals NHS Foundation Trust
University of Cambridge
Cambridge University Hospital NHS Foundation Trust
University of Edinburgh
Cambridge University NHS Foundation Trust and Cancer Research UK Cambridge Centre
Cambridge University Hospitals NHS Foundation Trust

Research output: Contribution to journal › Article › peer-review

17 Citations (Scopus)

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.

Original language	English
Pages (from-to)	391-396
Number of pages	6
Journal	Clinical Cancer Research
Volume	26
Issue number	2
DOIs	https://doi.org/10.1158/1078-0432.CCR-19-1729
Publication status	Published - 15 Jan 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

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

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10.1158/1078-0432.CCR-19-1729

Cite this

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title = "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.",

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author = "Casey, \{Ruth T\} and McLean, \{Mary A\} and Challis, \{Benjamin G\} and McVeigh, \{Terri P\} and Warren, \{Anne Y\} and Lee Mendil and Richard Houghton and \{De Sanctis\}, Stefano and Vasilis Kosmoliaptsis and Sandford, \{Richard N\} and Gallagher, \{Ferdia A\} and Maher, \{Eamonn R\}",

year = "2020",

month = jan,

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doi = "10.1158/1078-0432.CCR-19-1729",

language = "English",

volume = "26",

pages = "391--396",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

number = "2",

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TY - JOUR

T1 - Fumarate Metabolic Signature for the Detection of Reed Syndrome in Humans

AU - Casey, Ruth T

AU - McLean, Mary A

AU - Challis, Benjamin G

AU - McVeigh, Terri P

AU - Warren, Anne Y

AU - Mendil, Lee

AU - Houghton, Richard

AU - De Sanctis, Stefano

AU - Kosmoliaptsis, Vasilis

AU - Sandford, Richard N

AU - Gallagher, Ferdia A

AU - Maher, Eamonn R

PY - 2020/1/15

Y1 - 2020/1/15

N2 - 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.

AB - 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.

KW - Adult

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KW - Germ-Line Mutation

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KW - Leiomyomatosis/diagnosis

KW - Male

KW - Middle Aged

KW - Neoplastic Syndromes, Hereditary/diagnosis

KW - Proton Magnetic Resonance Spectroscopy/methods

KW - Skin Neoplasms/diagnosis

KW - Succinate Dehydrogenase/genetics

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UR - https://aacrjournals.org/clincancerres/article/26/2/391/82703/Fumarate-Metabolic-Signature-for-the-Detection-of

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SP - 391

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JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 2

ER -

Fumarate Metabolic Signature for the Detection of Reed Syndrome in Humans

Abstract

UN SDGs

Keywords

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