Summary of Study ST000821

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000585. The data can be accessed directly via it's Project DOI: 10.21228/M8239Z This work is supported by NIH grant, U2C- DK119886.

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Study IDST000821
Study TitleMetabolomic profiling of IDH1 mutation
Study TypeMS analysis
Study SummaryWe are interested in using both spontaneous and stimulated Raman microscopy to visualize these metabolomic changes as spectral alterations. We have two isogneic cell lines of normal human astrocytes differing only by a point mutation in the IDH-1 gene. We will work with the metabolomics core to elucidate the changes in central metabolism and lipid synthesys in an effort to determine the precise biochemical alterations underlying observed spectral differences. We wil then use a selective inhibitor of the IDH1 R132H to demonstrate to attempt to return TCA metabolome and lipidome to WT phenotype. Lastly, we will use a cell-permeablized variant of 2HG (2R-octyl-alpha-hydroxyglutarate) to recaptitulate the R132H mutant phenotype in wild-type cells, providing strong evidence that 2HG accumulation uderlies the metabolomic (and thus, spectral) changes observed.
Institute
University of Michigan
DepartmentBiomedical Research Core Facilities
LaboratoryMetabolomics core
Last NameKachman
First NameMaureen
Address6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714
Emailmkachman@med.umich.edu
Phone(734) 232-8175
Submit Date2017-07-14
Num Groups2
Total Subjects3
Study CommentsThe IDH-1 R132H mutation in low grade gliomas preceptitates oncogenesis through a neomorphic enzyme function: the reduction of alpha-ketoglutarate (aKG) to 2-hydroxygutarate (2HG). 2HG accumukates to extremely high (~100mM) concentrations in IDH1 mutant cells and has substantial, predictable metabolic effects, including inhibition of a-KG dependent dioxygenases and hypermethylation of histones and chromatin.
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2018-02-07
Release Version1
Maureen Kachman Maureen Kachman
https://dx.doi.org/10.21228/M8239Z
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR000585
Project DOI:doi: 10.21228/M8239Z
Project Title:Stimulated Raman Immunohistochemistry
Project Type:MS analysis
Project Summary:Profiling of WT, IDH1 R132H, WT + 2HG, Mut + AG!5198
Institute:University of Michigan
Department:Neurosurgery
Laboratory:Orringer Lab
Last Name:Orringer
First Name:Daniel
Address:Ann Arbor, MI
Email:dorringe@umich.edu
Phone:734-647-9222

Subject:

Subject ID:SU000847
Subject Type:HUMAN
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Mammals

Factors:

Subject type: HUMAN; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id IDH1_MUTATION_STATUS
SA045818S00026543R132H Mutant
SA045819S00026542R132H Mutant
SA045820S00026541R132H Mutant
SA045821S00026544R132H Mutant
SA045822S00026545R132H Mutant
SA045823S00026547R132H Mutant
SA045824S00026546R132H Mutant
SA045825S00026540R132H Mutant
SA045826S00026539R132H Mutant
SA045827S00026533WT
SA045828S00026532WT
SA045829S00026531WT
SA045830S00026534WT
SA045831S00026535WT
SA045832S00026538WT
SA045833S00026537WT
SA045834S00026536WT
SA045835S00026530WT
Showing results 1 to 18 of 18

Collection:

Collection ID:CO000841
Collection Summary:-
Sample Type:Astrocyte cells

Treatment:

Treatment ID:TR000861
Treatment Summary:-

Sample Preparation:

Sampleprep ID:SP000854
Sampleprep Summary:-
Sampleprep Protocol Filename:A037-2HG_cells_updated-20160721.pdf

Combined analysis:

Analysis ID AN001304
Analysis type MS
Chromatography type Reversed phase
Chromatography system Agilent
Column Waters Acquity HSS T3 (50 x 2.1mm,1.8um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Agilent 6490A QQQ
Ion Mode NEGATIVE
Units uM/ng protein

Chromatography:

Chromatography ID:CH000913
Instrument Name:Agilent
Column Name:Waters Acquity HSS T3 (50 x 2.1mm,1.8um)
Solvent A:100% water; 2 mM ammonium formate
Solvent B:100% acetonitrile; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS001197
Analysis ID:AN001304
Instrument Name:Agilent 6490A QQQ
Instrument Type:Triple quadrupole
MS Type:ESI
Ion Mode:NEGATIVE
Analysis Protocol File:A037-2HG_cells_updated-20160721.pdf
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