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Highly specific determination of IDH status using edited in vivo magnetic resonance spectroscopy.

ABSTRACT: Background:Mutations in the isocitrate dehydrogenase (IDH) enzyme affect 40% of gliomas and represent a major diagnostic and prognostic marker. The goals of this study were to evaluate the performance of noninvasive magnetic resonance spectroscopy (MRS) methods to determine the IDH status of patients with brain gliomas through detection of the oncometabolite 2-hydroxyglutarate (2HG) and to compare performance of these methods with DNA sequencing and tissue 2HG analysis. Methods:Twenty-four subjects with suspected diagnosis of low-grade glioma were included prospectively in the study. For all subjects, MRS data were acquired at 3T using 2 MRS methods, edited MRS using Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence and a PRESS sequence optimized for 2HG detection, using a volume of interest larger than 6 mL. IDH mutational status was determined by a combination of automated immunohistochemical analysis and Sanger sequencing. Levels of 2HG in tissue samples measured by gas chromatography-mass spectrometry were compared with those estimated by MRS. Results:Edited MRS provided 100% specificity and 100% sensitivity in the detection of 2HG. The 2HG levels estimated by this technique were in line with those derived from tissue samples. Optimized PRESS provided lower performance, in agreement with previous findings. Conclusions:Our results suggest that edited MRS is one of the most reliable tools to predict IDH mutation noninvasively, showing high sensitivity and specificity for 2HG detection. Integrating edited MRS in clinical practice may be highly beneficial for noninvasive diagnosis of glioma, prognostic assessment, and treatment planning.

SUBMITTER: Branzoli F

PROVIDER: S-EPMC6007442 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Highly specific determination of IDH status using edited in vivo magnetic resonance spectroscopy.

Branzoli Francesca F Di Stefano Anna Luisa AL Capelle Laurent L Ottolenghi Chris C Valabrègue Romain R Deelchand Dinesh K DK Bielle Franck F Villa Chiara C Baussart Bertrand B Lehéricy Stéphane S Sanson Marc M Marjanska Malgorzata M

Neuro-oncology 20180601 7

<h4>Background</h4>Mutations in the isocitrate dehydrogenase (IDH) enzyme affect 40% of gliomas and represent a major diagnostic and prognostic marker. The goals of this study were to evaluate the performance of noninvasive magnetic resonance spectroscopy (MRS) methods to determine the IDH status of patients with brain gliomas through detection of the oncometabolite 2-hydroxyglutarate (2HG) and to compare performance of these methods with DNA sequencing and tissue 2HG analysis.<h4>Methods</h4>Tw ...[more]

PMID: 29126125

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Project description:Medulloblastoma (MB) is the most common malignant brain tumor occurring in childhood and rarely found in adult. Based on transcriptome profile MB are currently classified into four major molecular groups reflecting a considerable biological heterogeneity: WNT-activated, SHH-activated, group 3 and group 4. Recently, DNA methylation profiling allowed the identification of additional subgroups within the four major molecular groups associated with different clinic-pathological and molecular features. Isocitrate Dehydrogenase-1 (IDH1) mutations have been described in several tumours, including gliomas, while in MB are exceptionally reported and not routinely investigated. By mean of magnetic resonance spectroscopy (MRS) we unequivocally assessed the presence the oncometabolite D-2-Hydroxyglutarate (2HG), a marker of IDH1 and IDH2 mutation, in a case of adult MB. Immunophenotypical work-up and methylation profiling assigned the diagnosis of MB, subclass SHH-A, and molecular testing revealed the presence of the non-canonical somatic IDH1(p.R132C) mutation and an additional GNAS mutation, also exceptionally described in MB. To our knowledge this is the first reported case of MB harboring both mutations together. Of note, tumour exhibited a heterogeneous phenotype with a tumour component displaying glial differentiation, with robust GFAP expression, and a component with conventional MB features and selective presence of GNAS mutation, suggesting coexistence of two different major tumour clones. These findings draw attention to the need of a deeper genetic characterization of MB in order to get insights into their biology and improve stratification and clinical management of the patients. Moreover, reported data underling the importance of performing MRS for the identification of IDH mutations in non-glial tumours. The use of throughput molecular profiling analysis and advanced medical imaging technology will certainly increase the frequency with which rare tumour entities will be identified. Whether they have any particular therapeutic implications or prognostic relevance requires further investigations.

Dataset Information

Highly specific determination of IDH status using edited in vivo magnetic resonance spectroscopy.

Publications

Highly specific determination of IDH status using edited in vivo magnetic resonance spectroscopy.

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