Summary of Study ST002734
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 PR001698. The data can be accessed directly via it's Project DOI: 10.21228/M8741T This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002734 |
| Study Title | Integrative multi-omics analysis of oncogenic EZH2 mutants: from epigenetic reprogramming to molecular signatures |
| Study Summary | The Enhancer of Zeste 2 Polycomb Repressive Complex 2 Subunit (EZH2) is an essential epigenetic modifier able to methylate lysine 27 on histone H3 (H3K27) to induce chromatin compaction, protein complex recruitment and ultimately transcriptional repression. Hematologic malignancies, including Diffuse Large B cell lymphoma (DLBCL) and Acute myeloid leukemia (AML) have shown a high EZH2-mutation frequency (>20%) associated with poor clinical outcomes. Particularly, two distinct oncogenic mutations, so-called gain-of-function (Y641F and A677G) and loss-of-function (H689A and F667I) are found in the catalytic domain of EZH2. In this study, a comprehensive multi-omics approach was employed to characterize downstream effects of H3K27me3 deposition driven by EZH2 mutations. Human embryonic kidney cells (HEK293T) were transfected to generate three stable isogenic EZH2 mutants: EZH2(Y641F), EZH2(A677G), and EZH2(H689A/F667I), which were validated via immunoblotting and DIA-MS-based histone profiling assay. Subsequently, constructs were analyzed under a comprehensive multi-omics approach including MS-based untargeted metabolomics, in positive and negative ionization MS/MS mode, acquired with an Agilent 6545 QTOF with a 1290 UHPLC system and HILIC column. A general dysregulation of mitochondrial processes, including TCA cycle and b-oxidation was common to all mutants. For EZH2(A677G) and EZH2(Y641F), alterations in methionine salvage pathway were predominant, while NAD+ pathways were highly disrupted in EZH2(H689A/F667I). |
| Institute | The Ohio State University |
| Department | Chemistry and Biochemistry |
| Last Name | Aldana |
| First Name | Julian |
| Address | 460 W 12th Ave, Columbus, OH 43210 |
| aldanaaroca.1@osu.edu | |
| Phone | +1 614-292-6136 |
| Submit Date | 2023-06-08 |
| Num Groups | 4 |
| Total Subjects | 12 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-08-01 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004432 | AN004433 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | HILIC |
| Chromatography system | Agilent 6545 QTOF | Agilent 6545 QTOF |
| Column | Phenomenex Kinetex HILIC (100 X 2.1mm, 2.6um) | Phenomenex Kinetex HILIC (100 X 2.1mm, 2.6um) |
| MS Type | ESI | ESI |
| MS instrument type | QTOF | QTOF |
| MS instrument name | Agilent 6545 QTOF | Agilent 6545 QTOF |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Peak area | Peak area |
