P02.18.B INTEGRATIVE OMICS ANALYSIS OF IDH1 MUTANT GLIOMA PATIENTS REVEALS ALTERATIONS IN BUTYRATE METABOLISM Article Swipe
Sabrina Fritah
,
Andrés Cano-Galiano
,
Réka Tóth
,
Ann‐Christin Hau
,
E Martinez-Garcia
,
Maria Francesca Allega
,
David Sumpton
,
Fred Fack
,
Monika Dieterle
,
Magretta Adiamah
,
Matthieu Gobin
,
Nathalie Nicot
,
Arnaud Muller
,
Tony Kaoma
,
Antoine Lesur
,
Michel Mittelbronn
,
Eric Van Dyck
,
Mahesh Bekal
,
Yoshua Esquenazi
,
Karsten Hiller
,
Per Øystein Sakariassen
,
Hrvoje Miletić
,
Gunnar Dittmar
,
Petr V. Nazarov
,
Saverio Tardito
,
Morten Lund‐Johansen
,
Rolf Bjerkvig
,
Anna Golebiewska
,
Simone P. Niclou
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1093/neuonc/noad137.103
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1093/neuonc/noad137.103
BACKGROUND Mutations in isocitrate dehydrogenase (IDH) 1 or 2 define glioma classification and determine the biology of these tumors. Although IDH is an essential enzyme in the cellular metabolism, powerful genome-wide analyses focus mostly at the genetic and epigenetic levels, while differences between distinct glioma entities at the proteomics, metabolomics, and functional levels are still poorly understood. Here, we provide an integrative multi-omics analysis of glioma patients to reveal metabolomic vulnerabilities of gliomas stratified by IDH mutation. MATERIAL AND METHODS We performed a multi-omics analysis of two cohorts of glioma patients (n=28) stratified based on IDH mutation status. Molecular assessment included LC-MS analysis, EPIC DNA methylation arrays, RNA-seq/HTA array-based transcriptomics and label-free quantitative proteomics. In 13 patients 13C-glucose was injected prior to surgery and tumor and adjacent brain tissue was collected. Gut microbial profiling using 16S ribosomal RNA (rRNA) sequencing was performed in a separate cohort of 128 glioma patients and 24 healthy individuals. Additional validation was performed in isogenic glioma stem-like cultures with CRISPR knock-in of IDH mutation. RESULTS We show that several molecular layers collectively contribute to biological differences between IDH mutant and wild-type gliomas, with strongest differences observed at the DNA methylation level. IDH mutant gliomas present specific molecular features linked to tumor metabolism. We confirm previous findings on 2-HG, cysteine and de novo glutathione synthesis pathways, which are specifically altered in IDH mutant gliomas. We further identify butyrate metabolism as a novel pathway highly active in IDH mutant gliomas. Butyrate is a bacterial metabolite with multiple systemic effects that is normally synthesized in the gut. This is supported by our gut microbiota metagenomics analysis of glioma patients. Yet the detection of enzymes associated with butyrate metabolism in tumor tissue and cell lines suggests a differential/enhanced metabolic rewiring of the butyrate signaling in IDH mutant gliomas CONCLUSION Our data shows the importance of multiple molecular layers in shaping specific features of IDH mutant gliomas. We unravel an activated butyrate metabolism in IDH mutant gliomas that may underly a novel gut-brain axis in glioma patients.
Related Topics
Concepts
Isocitrate dehydrogenase
Glioma
Biology
Metabolomics
IDH1
Proteomics
DNA methylation
Epigenetics
KEGG
Mutant
Computational biology
Genetics
Transcriptome
Cancer research
Bioinformatics
Biochemistry
Gene
Enzyme
Gene expression
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/neuonc/noad137.103
- OA Status
- green
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4386562652
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4386562652Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/neuonc/noad137.103Digital Object Identifier
- Title
-
P02.18.B INTEGRATIVE OMICS ANALYSIS OF IDH1 MUTANT GLIOMA PATIENTS REVEALS ALTERATIONS IN BUTYRATE METABOLISMWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-09-01Full publication date if available
- Authors
-
Sabrina Fritah, Andrés Cano-Galiano, Réka Tóth, Ann‐Christin Hau, E Martinez-Garcia, Maria Francesca Allega, David Sumpton, Fred Fack, Monika Dieterle, Magretta Adiamah, Matthieu Gobin, Nathalie Nicot, Arnaud Muller, Tony Kaoma, Antoine Lesur, Michel Mittelbronn, Eric Van Dyck, Mahesh Bekal, Yoshua Esquenazi, Karsten Hiller, Per Øystein Sakariassen, Hrvoje Miletić, Gunnar Dittmar, Petr V. Nazarov, Saverio Tardito, Morten Lund‐Johansen, Rolf Bjerkvig, Anna Golebiewska, Simone P. NiclouList of authors in order
- Landing page
-
https://doi.org/10.1093/neuonc/noad137.103Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://pmc.ncbi.nlm.nih.gov/articles/PMC10489582/pdf/noad137.103.pdfDirect OA link when available
- Concepts
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Isocitrate dehydrogenase, Glioma, Biology, Metabolomics, IDH1, Proteomics, DNA methylation, Epigenetics, KEGG, Mutant, Computational biology, Genetics, Transcriptome, Cancer research, Bioinformatics, Biochemistry, Gene, Enzyme, Gene expressionTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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10Other works algorithmically related by OpenAlex
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