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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST000821 |
| Study Title | Metabolomic profiling of IDH1 mutation |
| Study Type | MS analysis |
| Study Summary | We 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 |
| Department | Biomedical Research Core Facilities |
| Laboratory | Metabolomics core |
| Last Name | Kachman |
| First Name | Maureen |
| Address | 6300 Brehm Tower, 1000 Wall Street, Ann Arbor, MI 48105-5714 |
| mkachman@med.umich.edu | |
| Phone | (734) 232-8175 |
| Submit Date | 2017-07-14 |
| Num Groups | 2 |
| Total Subjects | 3 |
| Study Comments | The 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 Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2018-02-07 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
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 |
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 |
