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Series GSE96744 Query DataSets for GSE96744
Status Public on Apr 28, 2017
Title Epigenetic identity in AML is mostly dependent on disruption of non-promoter regulatory elements and reveals potentially antagonistic effects of mutations in epigenetic modifiers [mouse]
Platform organism Homo sapiens
Sample organisms Homo sapiens; Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Third-party reanalysis
Summary Aberrant DNA methylation of gene promoters is a hallmark of AML. To define more precisely how cytosine methylation is redistributed in AML, we performed base-pair resolution methylome sequencing in 119 patients. We find that leukemic DNA methylation patterning is tightly linked to somatic mutations and primarily driven by regulatory elements outside of promoters and by CpG shores as opposed to CpG islands. Active enhancers displayed much stronger focal differential methylation than promoters and were generally aberrantly hypomethylated except in IDH2 mutant and CEBPA silenced AMLs. AMLs with dominant hypermethylation feature greater epigenetic disruption of promoters. Those with dominant hypomethylation, such as DNMT3A mutated AMLs, display greater disruption of distal and intronic regions. IDH mutant AMLs manifest profound hypermethylation whereas DNMT3A mutant AMLs manifest profound hypomethylation of a different set of CpGs. In striking contrast, AMLs with co-occurring IDH1 and DNMT3A mutations exhibited epigenetic antagonism in which most CpGs affected by either mutation alone were no longer affected in the double mutant cases.
 
Overall design Enhanced Reduced Representation Bisulfite Sequencing (ERRBS) was performed on Idh2, Dnmt3a, and Idh2/Dnmt3a mutant mice. Idh2 mouse profiling is detailed in PMID: 28193779 and deposited here (LSK controls are deposited under GSE57114). Dnmt3a mutant and LSK control mouse profiling is detailed in PMID: 26710888 and deposited under GSE86827 with a set of LSK controls under GEO series GSE74165
 
Contributor(s) Glass JL, Garrett-Bakelman FE, Guryanova OA, Bowman R, Redlich S, Intlekofer AM, Meydan C, Fall M, Alonso A, Thompson CB, Levine R, Delwel R, Melnick A, Figueroa ME
Citation(s) 28408400
Submission date Mar 17, 2017
Last update date May 15, 2019
Contact name Jacob Lowell Glass
E-mail(s) glassj@mskcc.org
Organization name Memorial Sloan Kettering Cancer Center
Street address 1275 York Avenue
City New York
State/province NY
ZIP/Postal code 10065
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (7)
GSM2539358 IDH_V13
GSM2539359 IDH_V15
GSM2539360 IDH_V16
This SubSeries is part of SuperSeries:
GSE98350 Epigenetic identity in AML is mostly dependent on disruption of non-promoter regulatory elements and reveals potentially antagonistic effects of mutations in epigenetic modifiers
Relations
Reanalysis of GSM2309141
Reanalysis of GSM1375494
Reanalysis of GSM1375495
Reanalysis of GSM1375496
Reanalysis of GSM2309135
Reanalysis of GSM2309136
Reanalysis of GSM2309137
Reanalysis of GSM2309139
Reanalysis of GSM2309140
BioProject PRJNA384797
SRA SRP105425

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE96744_RAW.tar 113.4 Mb (http)(custom) TAR (of TXT)
GSE96744_mm10_dnmt3a.txt.gz 321.3 Kb (ftp)(http) TXT
GSE96744_mm10_idh2.txt.gz 532.1 Kb (ftp)(http) TXT
GSE96744_mm10_readme.txt.gz 872 b (ftp)(http) TXT
GSE96744_mm9_to_mm10_cpg.IDH_V13.mincov10.bed.gz 21.5 Mb (ftp)(http) BED
GSE96744_mm9_to_mm10_cpg.IDH_V13.mincov10.unmapped.txt.gz 778 b (ftp)(http) TXT
GSE96744_mm9_to_mm10_cpg.IDH_V15.mincov10.bed.gz 20.4 Mb (ftp)(http) BED
GSE96744_mm9_to_mm10_cpg.IDH_V15.mincov10.unmapped.txt.gz 707 b (ftp)(http) TXT
GSE96744_mm9_to_mm10_cpg.IDH_V16.mincov10.bed.gz 21.4 Mb (ftp)(http) BED
GSE96744_mm9_to_mm10_cpg.IDH_V16.mincov10.unmapped.txt.gz 720 b (ftp)(http) TXT
GSE96744_mm9_to_mm10_cpg.IDH_V17.mincov10.bed.gz 21.2 Mb (ftp)(http) BED
GSE96744_mm9_to_mm10_cpg.IDH_V17.mincov10.unmapped.txt.gz 782 b (ftp)(http) TXT
GSE96744_mm9_to_mm10_cpg.Sample_WT_LSK_A2.mincov10.bed.gz 26.7 Mb (ftp)(http) BED
GSE96744_mm9_to_mm10_cpg.Sample_WT_LSK_A2.mincov10.unmapped.txt.gz 982 b (ftp)(http) TXT
GSE96744_mm9_to_mm10_cpg.Sample_WT_LSK_A3.mincov10.bed.gz 27.3 Mb (ftp)(http) BED
GSE96744_mm9_to_mm10_cpg.Sample_WT_LSK_A3.mincov10.unmapped.txt.gz 1.0 Kb (ftp)(http) TXT
GSE96744_mm9_to_mm10_cpg.Sample_WT_LSK_A4.mincov10.bed.gz 27.7 Mb (ftp)(http) BED
GSE96744_mm9_to_mm10_cpg.Sample_WT_LSK_A4.mincov10.unmapped.txt.gz 1.2 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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