Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.
Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy.
Department of Radiology &Biomedical Imaging, University of California, San Francisco, CA, USA.
Llewellyn E
LE
Jalbert
Department of Radiology &Biomedical Imaging, University of California, San Francisco, CA, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
Adam
A
Elkhaled
Department of Pathology, University of California, San Francisco, CA, USA.|Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Joanna J
JJ
Phillips
Department of Radiology &Biomedical Imaging, University of California, San Francisco, CA, USA.
Evan
E
Neill
Department of Radiology &Biomedical Imaging, University of California, San Francisco, CA, USA.
Aurelia
A
Williams
Department of Radiology &Biomedical Imaging, University of California, San Francisco, CA, USA.
Jason C
JC
Crane
Department of Radiology &Biomedical Imaging, University of California, San Francisco, CA, USA.
Marram P
MP
Olson
Department of Neurological Surgery, University of California, San Francisco, CA, USA.|Department of Biostatistics and Epidemiology, University of California, San Francisco, CA, USA.
Annette M
AM
Molinaro
Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Mitchel S
MS
Berger
Department of Radiology &Biomedical Imaging, University of California, San Francisco, CA, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
John
J
Kurhanewicz
Department of Radiology &Biomedical Imaging, University of California, San Francisco, CA, USA.
Sabrina M
SM
Ronen
Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Susan M
SM
Chang
Department of Radiology &Biomedical Imaging, University of California, San Francisco, CA, USA.|Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
Sarah J
SJ
Nelson
D001706:Biopsy; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging
D007521:Isocitrate Dehydrogenase