 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Dec 03, 2010 |
| Title |
Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Methylation profiling by genome tiling array
|
| Summary |
Cancer-associated IDH mutations are characterized by neomorphic enzyme activity and resultant 2 hydroxyglutarate (2HG) production. Mutational and epigenetic profiling of a large AML patient cohort revealed that IDH1/2-mutant AMLs display global DNA hypermethylation and a specific hypermethylation signature. Furthermore, expression of 2HG-producing IDH alleles in cells rapidly induced global DNA hypermethylation. In the AML cohort, IDH1/2 mutations were mutually exclusive with mutations in the α-ketoglutarate-dependent enzyme TET2, and TET2 loss-of function mutations associated with similar epigenetic defects as IDH1/2 mutants. Consistent with these genetic and epigenetic data, expression of IDH mutants impaired TET2 catalytic function in cells. Finally, either expression of mutant IDH1/2 or Tet2 depletion impaired hematopoietic differentiation and increased stem cell marker expression, suggesting a shared pro-leukemogenic effect.
|
| |
|
| Overall design |
DNA methylation and gene expression profiling in IDH1/2 mutant vs. IDH1/2 wild-type AML
|
| |
|
| Contributor(s) |
Figueroa ME, Melnick A |
| Citation(s) |
21130701, 22855599, 27446991 |
| Submission date |
Oct 04, 2010 |
| Last update date |
Apr 19, 2019 |
| Contact name |
Maria Eugenia Figueroa |
| E-mail(s) |
mef162@miami.edu
|
| Organization name |
University of Miiami
|
| Department |
Human Genetics
|
| Lab |
Maria Figueroa
|
| Street address |
1501 NW 10th Ave, BRB 709A, Locator code C227
|
| City |
Miami |
| State/province |
FL |
| ZIP/Postal code |
33136 |
| Country |
USA |
| |
|
| Platforms (2) |
|
| Samples (757)
|
|
| Relations |
| BioProject |
PRJNA132611 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE24505_RAW.tar |
6.9 Gb |
(http)(custom) |
TAR (of PAIR) |
| GSE24505_sample_names_and_accessions.txt.gz |
3.9 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...