2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas

Mutations in isocitrate dehydrogenases 1 and 2 ( IDH1 and IDH2 ) in the majority of people with grade 2 and 3 gliomas is associated with elevated levels of 2-hydroxyglutarate (2HG) within the tumor. As harboring IDH1 or IDH2 mutations confers a considerable survival benefit in these individuals, the...

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Published in	Nature medicine Vol. 18; no. 4; pp. 624 - 629
Main Authors	Choi, Changho, Ganji, Sandeep K, DeBerardinis, Ralph J, Hatanpaa, Kimmo J, Rakheja, Dinesh, Kovacs, Zoltan, Yang, Xiao-Li, Mashimo, Tomoyuki, Raisanen, Jack M, Marin-Valencia, Isaac, Pascual, Juan M, Madden, Christopher J, Mickey, Bruce E, Malloy, Craig R, Bachoo, Robert M, Maher, Elizabeth A
Format	Journal Article
Language	English
Published	New York Nature Publishing Group US 01.04.2012 Nature Publishing Group
Subjects	631/208/737 692/699/375/1922 692/700/1421/1628 Algorithms Aspartic Acid - analogs & derivatives Aspartic Acid - metabolism Biomedical and Life Sciences Biomedicine Brain - enzymology Brain cancer Brain Mapping Brain Neoplasms - genetics Brain Neoplasms - metabolism Cancer Research Choline - metabolism Creatine - metabolism Enzymes Female Gene expression Glioma - genetics Glioma - metabolism Glutarates Humans Infectious Diseases Isocitrate Dehydrogenase - genetics Magnetic Resonance Spectroscopy Male Mass spectrometry Medical imaging Metabolic Diseases Molecular Medicine Mutation Mutation - genetics Neurosciences Spectroscopy Spectrum analysis Statistics as Topic technical-report Tumors
Online Access	Get full text
ISSN	1078-8956 1546-170X 1546-170X
DOI	10.1038/nm.2682

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Abstract	Mutations in isocitrate dehydrogenases 1 and 2 ( IDH1 and IDH2 ) in the majority of people with grade 2 and 3 gliomas is associated with elevated levels of 2-hydroxyglutarate (2HG) within the tumor. As harboring IDH1 or IDH2 mutations confers a considerable survival benefit in these individuals, there has been considerable interest in studying this metabolite as a potential biomarker. Here, Changho Choi et al . report the successful noninvasive detection of 2HG in 30 subjects with gliomas using a proton magnetic resonance spectroscopy approach. Mutations in isocitrate dehydrogenases 1 and 2 ( IDH1 and IDH2 ) have been shown to be present in most World Health Organization grade 2 and grade 3 gliomas in adults. These mutations are associated with the accumulation of 2-hydroxyglutarate (2HG) in the tumor. Here we report the noninvasive detection of 2HG by proton magnetic resonance spectroscopy (MRS). We developed and optimized the pulse sequence with numerical and phantom analyses for 2HG detection, and we estimated the concentrations of 2HG using spectral fitting in the tumors of 30 subjects. Detection of 2HG correlated with mutations in IDH1 or IDH2 and with increased levels of D -2HG by mass spectrometry of the resected tumors. Noninvasive detection of 2HG may prove to be a valuable diagnostic and prognostic biomarker.
AbstractList	Mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) have been shown to be present in most World Health Organization grade 2 and grade 3 gliomas in adults. These mutations are associated with the accumulation of 2-hydroxyglutarate (2HG) in the tumor. Here we report the noninvasive detection of 2HG by proton magnetic resonance spectroscopy (MRS). We developed and optimized the pulse sequence with numerical and phantom analyses for 2HG detection, and we estimated the concentrations of 2HG using spectral fitting in the tumors of 30 subjects. Detection of 2HG correlated with mutations in IDH1 or IDH2 and with increased levels of D-2HG by mass spectrometry of the resected tumors. Noninvasive detection of 2HG may prove to be a valuable diagnostic and prognostic biomarker. Mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) have been shown to be present in most World Health Organization grade 2 and grade 3 gliomas in adults. These mutations are associated with the accumulation of 2-hydroxyglutarate (2HG) in the tumor. Here we report the noninvasive detection of 2HG by proton magnetic resonance spectroscopy (MRS). We developed and optimized the pulse sequence with numerical and phantom analyses for 2HG detection, and we estimated the concentrations of 2HG using spectral fitting in the tumors of 30 subjects. Detection of 2HG correlated with mutations in IDH1 or IDH2 and with increased levels of D-2HG by mass spectrometry of the resected tumors. Noninvasive detection of 2HG may prove to be a valuable diagnostic and prognostic biomarker. [PUBLICATION ABSTRACT] Mutations in isocitrate dehydrogenases 1 and 2 ( IDH1 and IDH2 ) in the majority of people with grade 2 and 3 gliomas is associated with elevated levels of 2-hydroxyglutarate (2HG) within the tumor. As harboring IDH1 or IDH2 mutations confers a considerable survival benefit in these individuals, there has been considerable interest in studying this metabolite as a potential biomarker. Here, Changho Choi et al . report the successful noninvasive detection of 2HG in 30 subjects with gliomas using a proton magnetic resonance spectroscopy approach. Mutations in isocitrate dehydrogenases 1 and 2 ( IDH1 and IDH2 ) have been shown to be present in most World Health Organization grade 2 and grade 3 gliomas in adults. These mutations are associated with the accumulation of 2-hydroxyglutarate (2HG) in the tumor. Here we report the noninvasive detection of 2HG by proton magnetic resonance spectroscopy (MRS). We developed and optimized the pulse sequence with numerical and phantom analyses for 2HG detection, and we estimated the concentrations of 2HG using spectral fitting in the tumors of 30 subjects. Detection of 2HG correlated with mutations in IDH1 or IDH2 and with increased levels of D -2HG by mass spectrometry of the resected tumors. Noninvasive detection of 2HG may prove to be a valuable diagnostic and prognostic biomarker. Mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) have been shown to be present in most World Health Organization grade 2 and grade 3 gliomas in adults. These mutations are associated with the accumulation of 2-hydroxyglutarate (2HG) in the tumor. Here we report the noninvasive detection of 2HG by proton magnetic resonance spectroscopy (MRS). We developed and optimized the pulse sequence with numerical and phantom analyses for 2HG detection, and we estimated the concentrations of 2HG using spectral fitting in the tumors of 30 subjects. Detection of 2HG correlated with mutations in IDH1 or IDH2 and with increased levels of D-2HG by mass spectrometry of the resected tumors. Noninvasive detection of 2HG may prove to be a valuable diagnostic and prognostic biomarker.Mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) have been shown to be present in most World Health Organization grade 2 and grade 3 gliomas in adults. These mutations are associated with the accumulation of 2-hydroxyglutarate (2HG) in the tumor. Here we report the noninvasive detection of 2HG by proton magnetic resonance spectroscopy (MRS). We developed and optimized the pulse sequence with numerical and phantom analyses for 2HG detection, and we estimated the concentrations of 2HG using spectral fitting in the tumors of 30 subjects. Detection of 2HG correlated with mutations in IDH1 or IDH2 and with increased levels of D-2HG by mass spectrometry of the resected tumors. Noninvasive detection of 2HG may prove to be a valuable diagnostic and prognostic biomarker.
Author	Maher, Elizabeth A Ganji, Sandeep K Choi, Changho Hatanpaa, Kimmo J Raisanen, Jack M Rakheja, Dinesh Yang, Xiao-Li Mashimo, Tomoyuki Bachoo, Robert M Kovacs, Zoltan Malloy, Craig R Marin-Valencia, Isaac Pascual, Juan M DeBerardinis, Ralph J Madden, Christopher J Mickey, Bruce E
Author_xml	– sequence: 1 givenname: Changho surname: Choi fullname: Choi, Changho email: changho.choi@utsouthwestern.edu organization: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Department of Radiology, University of Texas Southwestern Medical Center – sequence: 2 givenname: Sandeep K surname: Ganji fullname: Ganji, Sandeep K organization: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Department of Radiology, University of Texas Southwestern Medical Center – sequence: 3 givenname: Ralph J surname: DeBerardinis fullname: DeBerardinis, Ralph J organization: Department of Pediatrics, University of Texas Southwestern Medical Center, McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center – sequence: 4 givenname: Kimmo J surname: Hatanpaa fullname: Hatanpaa, Kimmo J organization: Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Department of Pathology, University of Texas Southwestern Medical Center, Annette Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center – sequence: 5 givenname: Dinesh surname: Rakheja fullname: Rakheja, Dinesh organization: Department of Pathology, University of Texas Southwestern Medical Center, Children’s Medical Center – sequence: 6 givenname: Zoltan surname: Kovacs fullname: Kovacs, Zoltan organization: Advanced Imaging Research Center, University of Texas Southwestern Medical Center – sequence: 7 givenname: Xiao-Li surname: Yang fullname: Yang, Xiao-Li organization: Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Annette Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Department of Internal Medicine, University of Texas Southwestern Medical Center – sequence: 8 givenname: Tomoyuki surname: Mashimo fullname: Mashimo, Tomoyuki organization: Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Annette Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Department of Internal Medicine, University of Texas Southwestern Medical Center – sequence: 9 givenname: Jack M surname: Raisanen fullname: Raisanen, Jack M organization: Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Department of Pathology, University of Texas Southwestern Medical Center, Annette Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center – sequence: 10 givenname: Isaac surname: Marin-Valencia fullname: Marin-Valencia, Isaac organization: Department of Pediatrics, University of Texas Southwestern Medical Center – sequence: 11 givenname: Juan M surname: Pascual fullname: Pascual, Juan M organization: Department of Pediatrics, University of Texas Southwestern Medical Center, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Department of Physiology, University of Texas Southwestern Medical Center – sequence: 12 givenname: Christopher J surname: Madden fullname: Madden, Christopher J organization: Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Annette Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Department of Neurological Surgery, University of Texas Southwestern Medical Center – sequence: 13 givenname: Bruce E surname: Mickey fullname: Mickey, Bruce E organization: Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Annette Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Department of Neurological Surgery, University of Texas Southwestern Medical Center – sequence: 14 givenname: Craig R surname: Malloy fullname: Malloy, Craig R organization: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Department of Radiology, University of Texas Southwestern Medical Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Veterans Affairs North Texas Health Care System – sequence: 15 givenname: Robert M surname: Bachoo fullname: Bachoo, Robert M organization: Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Annette Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center – sequence: 16 givenname: Elizabeth A surname: Maher fullname: Maher, Elizabeth A email: elizabeth.maher@utsouthwestern.edu organization: Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Annette Strauss Center for Neuro-Oncology, University of Texas Southwestern Medical Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/22281806$$D View this record in MEDLINE/PubMed
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ContentType	Journal Article
Copyright	Springer Nature America, Inc. 2009 Copyright Nature Publishing Group Apr 2012
Copyright_xml	– notice: Springer Nature America, Inc. 2009 – notice: Copyright Nature Publishing Group Apr 2012
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Snippet	Mutations in isocitrate dehydrogenases 1 and 2 ( IDH1 and IDH2 ) in the majority of people with grade 2 and 3 gliomas is associated with elevated levels of... Mutations in isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) have been shown to be present in most World Health Organization grade 2 and grade 3 gliomas in...
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SubjectTerms	631/208/737 692/699/375/1922 692/700/1421/1628 Algorithms Aspartic Acid - analogs & derivatives Aspartic Acid - metabolism Biomedical and Life Sciences Biomedicine Brain - enzymology Brain cancer Brain Mapping Brain Neoplasms - genetics Brain Neoplasms - metabolism Cancer Research Choline - metabolism Creatine - metabolism Enzymes Female Gene expression Glioma - genetics Glioma - metabolism Glutarates Humans Infectious Diseases Isocitrate Dehydrogenase - genetics Magnetic Resonance Spectroscopy Male Mass spectrometry Medical imaging Metabolic Diseases Molecular Medicine Mutation Mutation - genetics Neurosciences Spectroscopy Spectrum analysis Statistics as Topic technical-report Tumors
Title	2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas
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