NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE25706 Query DataSets for GSE25706
Status Public on Dec 11, 2010
Title Epigenome analysis of patients with various myeloid malignancies including differential levels of 5-hydroxymethylcytosine
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary TET2 is a close relative of TET1, an enzyme that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. The gene encoding TET2 resides at chromosome 4q24, in a region showing recurrent microdeletions and copy-neutral loss of heterozygosity (CN-LOH) in patients with diverse myeloid malignancies. Somatic TET2 mutations are frequently observed in myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes including chronic myelomonocytic leukaemia (CMML), acute myeloid leukaemias (AML) and secondary AML (sAML). We show here that TET2 mutations associated with myeloid malignancies compromise catalytic activity. Bone marrow samples from patients with TET2 mutations displayed uniformly low levels of 5hmC in genomic DNA compared to bone marrow samples from healthy controls. Moreover, small hairpin RNA (shRNA)-mediated depletion of Tet2 in mouse haematopoietic precursors skewed their differentiation towards monocyte/macrophage lineages in culture. There was no significant difference in DNA methylation between bone marrow samples from patients with high 5hmC versus healthy controls, but samples from patients with low 5hmC showed hypomethylation relative to controls at the majority of differentially methylated CpG sites. Our results demonstrate that Tet2 is important for normal myelopoiesis, and suggest that disruption of TET2 enzymatic activity favours myeloid tumorigenesis. Measurement of 5hmC levels in myeloid malignancies may prove valuable as a diagnostic and prognostic tool, to tailor therapies and assess responses to anticancer drugs.
 
Overall design Genome wide DNA methylation profiling of patients samples with various myeloid malignancies and diffrential levels of 5hmC.The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in bone marrow samples and occasionally peripheral blood samples. Samples included 28 control healthy bone marrows, 29 patients samples with low 5hmC levels (7 patients with wild-type TET2 and 22 mutant TET2) and 24 with high levels of 5hmC (22 with wild-type TET2 and 2 mutant TET2).
Bisulphite converted DNA from 81 samples was hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2
 
Contributor(s) Jankowska AM, Ganetzky R, Maciejewski JP
Citation(s) 21057493
Submission date Nov 30, 2010
Last update date Jan 02, 2015
Contact name Anna M Jankowska
E-mail(s) jankowa@ccf.org
Phone 216-24458783
Organization name Cleveland Clinic,Taussig Cancer Institute
Department THOR
Street address 9500 Euclid Ave.
City Cleveland
State/province Ohio
ZIP/Postal code 44195
Country USA
 
Platforms (1)
GPL8490 Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2)
Samples (81)
GSM637990 genomic DNA from healthy bone marrow #CCF042
GSM637991 genomic DNA from healthy bone marrow #CCF122
GSM637992 genomic DNA from healthy bone marrow #CCF044
Relations
BioProject PRJNA133821

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
GSE25706_RAW.tar 5.8 Mb (http)(custom) TAR
GSE25706_raw_data.txt.gz 9.9 Mb (ftp)(http) TXT
Processed data included within Sample table
| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap