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

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

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

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

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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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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 - Kidney Neoplasms/diagnosis

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

KW - Uterine Neoplasms/diagnosis

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

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VL - 26

SP - 391

EP - 396

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 2

ER -

Fumarate Metabolic Signature for the Detection of Reed Syndrome in Humans

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