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.

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Study IDST002734
Study TitleIntegrative multi-omics analysis of oncogenic EZH2 mutants: from epigenetic reprogramming to molecular signatures
Study SummaryThe 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
DepartmentChemistry and Biochemistry
Last NameAldana
First NameJulian
Address460 W 12th Ave, Columbus, OH 43210
Emailaldanaaroca.1@osu.edu
Phone+1 614-292-6136
Submit Date2023-06-08
Num Groups4
Total Subjects12
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2023-08-01
Release Version1
Julian Aldana Julian Aldana
https://dx.doi.org/10.21228/M8741T
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

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

mb_sample_id local_sample_id Genotype
SA288553A677G_2_negA677G-mutant
SA288554A677G_3_negA677G-mutant
SA288555A677G_1A677G-mutant
SA288556A677G_1_negA677G-mutant
SA288557A677G_2A677G-mutant
SA288558A677G_3A677G-mutant
SA288559DM_1F667I/H689A-mutant
SA288560DM_3F667I/H689A-mutant
SA288561DM_2_negF667I/H689A-mutant
SA288562DM_3_negF667I/H689A-mutant
SA288563DM_2F667I/H689A-mutant
SA288564DM_1_negF667I/H689A-mutant
SA288565QC_2_negQuality control
SA288566QC_3_negQuality control
SA288567QC_1_negQuality control
SA288568QC_4_negQuality control
SA288569QC_0_negQuality control
SA288570QC_0Quality control
SA288571QC_2Quality control
SA288572QC_3Quality control
SA288573QC_4Quality control
SA288574QC_1Quality control
SA288575WT_3_negWild-type
SA288576WT_1_negWild-type
SA288577WT_2_negWild-type
SA288578WT_1Wild-type
SA288579WT_3Wild-type
SA288580WT_2Wild-type
SA288581Y641F_1Y641F-mutant
SA288582Y641F_1_negY641F-mutant
SA288583Y641F_2Y641F-mutant
SA288584Y641F_3Y641F-mutant
SA288585Y641F_2_negY641F-mutant
SA288586Y641F_3_negY641F-mutant
Showing results 1 to 34 of 34
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