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Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate
Ovidiu C. Andronesi, Otto Rapalino, Elizabeth Gerstner, Andrew Chi, Tracy T. Batchelor, Dan P. Cahill, A. Gregory Sorensen, Bruce R. Rosen
Ovidiu C. Andronesi, Otto Rapalino, Elizabeth Gerstner, Andrew Chi, Tracy T. Batchelor, Dan P. Cahill, A. Gregory Sorensen, Bruce R. Rosen
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Review Series

Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate

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Abstract

The investigation of metabolic pathways disturbed in isocitrate dehydrogenase (IDH) mutant tumors revealed that the hallmark metabolic alteration is the production of D-2-hydroxyglutarate (D-2HG). The biological impact of D-2HG strongly suggests that high levels of this metabolite may play a central role in propagating downstream the effects of mutant IDH, leading to malignant transformation of cells. Hence, D-2HG may be an ideal biomarker for both diagnosing and monitoring treatment response targeting IDH mutations. Magnetic resonance spectroscopy (MRS) is well suited to the task of noninvasive D-2HG detection, and there has been much interest in developing such methods. Here, we review recent efforts to translate methodology using MRS to reliably measure in vivo D-2HG into clinical research.

Authors

Ovidiu C. Andronesi, Otto Rapalino, Elizabeth Gerstner, Andrew Chi, Tracy T. Batchelor, Dan P. Cahill, A. Gregory Sorensen, Bruce R. Rosen

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Figure 1

In vivo D-2HG measurements: (A) J-difference spectroscopy with MEGA-LASER sequence in a patient with GBM with mutant IDH1.

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In vivo D-2HG measurements: (A) J-difference spectroscopy with MEGA-LASE...
Adapted with permission from Science Translational Medicine (29). (B) Spectral editing with PRESS sequence of TE 97 ms (TE1: 32 ms, TE2: 65 ms) in a patient with mutant IDH1 oligodendroglioma. Adapted with permission from Nature Medicine (30). (C) Spectra acquired with PRESS sequence of TE 30 ms in a patient with mutant IDH1 anaplastic astrocytoma. Adapted with permission from Journal of Neuro-Oncology (24). Cho, choline; Cre, creatine; Gln, glutamine; Glu, glutamate; Lac, lactate; MM, macromolecules; NAA, N-acetyl-aspartate.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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