| Accession |
PRJCA000102 |
| Title |
Loss of 5-hydroxymethylcytosine is linked to gene body hypermethylation in kidney cancer |
| Relevance |
Medical |
| Umbrella project |
eGPS: evolutionary Genotype-Phenotype Systems biology
Key theories & Model
The driving effect of DNA methylation on complex traits
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| Data types |
Epigenomics
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| Organisms |
Homo sapiens
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| Description |
Both 5-methylcytosine (5mC) and its oxidized form, 5-hydroxymethylcytosine (5hmC), have been proposed to be involved in tumorigenesis. Because the readout of the broadly used 5mC mapping method, bisulfite sequencing (BS-seq), is the sum of 5mC and 5hmC levels, the aberrant patterns and interdependence of these two modifications separately remain poorly understood. By profiling real 5mC (BS-seq corrected by Tet-assisted bisulfite sequencing, TAB-seq) and 5hmC (TAB-seq) levels simultaneously at single nucleotide resolution, we here demonstrated that there is no global loss of 5mC in kidney tumors compared with matched normal tissues. Conversely, 5hmC was globally lost in virtually all kidney tumor tissues. The 5hmC level in tumor tissues was an independent prognostic marker for kidney cancer, with lower levels of 5hmC associated with shorter overall survival. Furthermore, we demonstrated that loss of 5hmC is linked to hypermethylation in tumors compared with matched normal tissues, particularly in gene body regions. Strikingly, gene body hypermethylation was significantly associated with silencing of tumor-related genes that for a few examples. Down-regulation of IDH1 was identified as a mechanism underlying 5hmC loss in kidney cancer. Rescuing 5hmC levels attenuated the invasion capacity of tumor cells and suppressed tumor growth in a xenograft model. Collectively, our results demonstrate that loss of 5hmC is both a prognostic marker and an oncogenic event in kidney cancer by remodeling the DNA methylation pattern |
| Sample scope |
carcinoma |
| Release date |
2016-03-18 |
| Publication |
| PubMed ID |
Article title |
Journal name |
DOI |
Year |
| 26680004
|
Loss of 5-hydroxymethylcytosine is linked to gene body hypermethylation in kidney cancer.
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Cell Research
|
10.1038/cr.2015.150
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2016
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| Data provider |
| Data provider |
Data provider URL |
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| Grants |
| Agency |
program |
Grant ID |
Grant title |
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| Chinese Academy of Sciences (CAS)
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Strategic Priority Research Program of Chinese Academy of Sciences (CAS)
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XDB13000000
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| Accessions in other database |
| Accession |
Database name |
| GSE63183
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NCBI
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| External link |
| External link |
Link description |
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| Submitter |
ZhengZheng
Xu (xdzperfect@163.com)
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| Organization |
Beijing Institute of Genomics, Chinese Academy of Sciences |
| Submission date |
2015-11-17 |
