title: Magnetic resonance of 2-hydroxyglutarate in IDH1-mutated low-grade gliomas.
abstract: Recent studies have indicated that a significant survival advantage is conferred to patients with gliomas whose lesions harbor mutations in the genes isocitrate dehydrogenase 1 and 2 (IDH1/2). IDH1/2 mutations result in aberrant enzymatic production of the potential oncometabolite D-2-hydroxyglutarate (2HG). Here, we report on the ex vivo detection of 2HG in IDH1-mutated tissue samples from patients with recurrent low-grade gliomas using the nuclear magnetic resonance technique of proton high-resolution magic angle spinning spectroscopy. Relative 2HG levels from pathologically confirmed mutant IDH1 tissues correlated with levels of other ex vivo metabolites and histopathology parameters associated with increases in mitotic activity, relative tumor content, and cellularity. Ex vivo spectroscopic measurements of choline-containing species and in vivo magnetic resonance measurements of diffusion parameters were also correlated with 2HG levels. These data provide extensive characterization of mutant IDH1 lesions while confirming the potential diagnostic value of 2HG as a surrogate marker of patient survival. Such information may augment the ability of clinicians to monitor therapeutic response and provide criteria for stratifying patients to specific treatment regimens.
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Elkhaled
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Llewellyn E
authors.initials: LE
authors.lastname: Jalbert
authors.affiliation: Department of Pathology, University of California, San Francisco, San Francisco, CA 94158, USA.|Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Joanna J
authors.initials: JJ
authors.lastname: Phillips
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Hikari A I
authors.initials: HAI
authors.lastname: Yoshihara
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94158, USA.|Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Rupa
authors.initials: R
authors.lastname: Parvataneni
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Radhika
authors.initials: R
authors.lastname: Srinivasan
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Bourne
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Soonmee
authors.initials: S
authors.lastname: Cha
authors.affiliation: Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94158, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Nelson
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D004252:DNA Mutational Analysis; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism* / Q000601:surgery; D005977:Glutarates / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007521:Isocitrate Dehydrogenase / Q000737:chemistry / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D060787:Neoplasm Grading; D019047:Phantoms, Imaging; D014944:World Health Organization
chemical_list: D005977:Glutarates; C019417:alpha-hydroxyglutarate; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human