Rapid detection of 2-hydroxyglutarate in frozen sections of IDH mutant tumors by MALDI-TOF mass spectrometry

Longuespée, Rémi; Wefers, Annika K.; Vita, Elena De; Miller, Aubry K.; Reuß, David; Wick, Wolfgang; Herold‐Mende, Christel; Kriegsmann, Mark; Schirmacher, Peter; Deimling, Andreas von; Pusch, Stefan

doi:10.1186/s40478-018-0523-3

Cited by 32 publications

(39 citation statements)

References 25 publications

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“…Areas of application of the MALDI‐MSI are mainly pathology, medical, pharmaceutical, and fundamental research . In addition, MALDI‐MSI is gaining interest for the detection of metabolites in frozen tissue sections in a diagnostic setting . Fast MALDI‐MSI instruments as the Bruker rapifleX MALDI Tissuetyper have the potential to offer a supporting tool for diagnostics and decision‐making during surgeries.…”

Section: Discussionmentioning

confidence: 99%

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Immersion by rotation‐based application of the matrix for fast and reproducible sample preparations and robust results in mass spectrometry imaging

Schäfermann

Kliewer

Lösch³

et al. 2020

J Mass Spectrom

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Automated matrix deposition for matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is crucial for producing reproducible analyte ion signals. Here we report an innovative method employing an automated immersion apparatus, which enables a robust matrix deposition within 5 minutes and with scalable throughput by using MAPS matrix and non‐polar solvents. MSI results received from mouse heart and rat brain tissues were qualitatively similar to those from nozzle sprayed samples with respect to peak number and quality of the ion images. Overall, the immersion‐method enables a fast and careful matrix deposition and has the future potential for implementation in clinical tissue diagnostics.

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Section: Discussionmentioning

confidence: 99%

“…41 In addition, MALDI-MSI is gaining interest for the detection of metabolites in frozen tissue sections in a diagnostic setting. 42 Fast…”

Section: Discussionmentioning

confidence: 99%

Immersion by rotation‐based application of the matrix for fast and reproducible sample preparations and robust results in mass spectrometry imaging

Schäfermann

Kliewer

Lösch³

et al. 2020

J Mass Spectrom

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“…The specific nature of IDH mutation in gliomas may be further exploited for 2‐HG‐targeting diagnostics and biomarkers (Fig. ) . Further data are required to establish the role of IDH mutation and 2‐HG in clinical diagnostics and therapeutics.…”

Section: Molecular Therapies Targeting Mutation‐dependent Metabolism mentioning

confidence: 99%

“…5). [64][65][66] Further data are required to establish the role of IDH mutation and 2-HG in clinical diagnostics and therapeutics.…”

Section: Molecular Therapies Targeting Mutation-dependent Metabolism mentioning

confidence: 99%

Metabolic reprogramming in the pathogenesis of glioma: Update

et al. 2019

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Cancer is a genetic disease that is currently classified not only by its tissue and cell type of origin but increasingly by its molecular composition. Increasingly, tumor classification and subtyping is being performed based upon the oncogene gains, tumor suppressor losses, and associated epigenetic and transcriptional features. However, cancers, including brain tumors, are also characterized by profound alterations in cellular metabolism. At present, even though signature mutations in known metabolic enzymes are recognized as being important, the metabolic landscape of tumors is not currently incorporated into tumor diagnostic categories. Here we describe a set of recent discoveries on metabolic reprogramming driven by mutations in the genes for the isocitrate dehydrogenase (IDH) and receptor tyrosine kinase (RTK) pathways, which are the most commonly observed aberrations in diffuse gliomas. We highlight the importance of oncometabolites to dynamically shift the epigenetic landscape in IDH‐mutant gliomas, and c‐Myc and mechanistic target of rapamycin (mTOR) complexes in RTK‐mutated gliomas to adapt to the microenvironment through metabolic reprogramming. These signify the integration of the genetic mutations with metabolic reprogramming and epigenetic shifts in diffuse gliomas, shedding new light onto potential patient subsets, coupled with information to guide the development of new therapeutic opportunities against the deadly types of brain tumors.

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“…Today, four approaches appear as possible future cornerstones for histoproteomic diagnostics in institutes of pathology: MALDI profiling and imaging, liquid chromatography‐tandem mass spectrometry (LC‐MS/MS), and laser microdissection–based microproteomics . MALDI profiling was recently demonstrated as a reliable approach for rapid diagnosis with the evaluation of isocitrate dehydrogenase mutational status in diffuse gliomas . MALDI imaging allows for close correlation between histological structures and mass spectrometric measurements .…”

mentioning

confidence: 99%