Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation

被引：475

作者：

Yang, H. ^{[1
,2
]}

Liu, Y. ^{[3
,4
]}

Bai, F. ^{[5
]}

Zhang, J-Y ^{[1
]}

Ma, S-H ^{[1
,2
]}

Liu, J. ^{[3
,4
]}

Xu, Z-D ^{[3
,4
]}

Zhu, H-G ^{[3
,4
]}

Ling, Z-Q ^{[6
]}

Ye, D. ^{[1
]}

Guan, K-L ^{[1
,4
,7
]}

Xiong, Y. ^{[1
,2
,5
]}

机构：

[1] Fudan Univ, Mol & Cell Biol Lab, Inst Biomed Sci, Shanghai 200433, Peoples R China

[2] Fudan Univ, Coll Life Sci, Shanghai 200433, Peoples R China

[3] Fudan Univ, Dept Pathol, Shanghai 200433, Peoples R China

[4] Fudan Univ, Shanghai Med Coll, Shanghai 200433, Peoples R China

[5] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA

[6] Zhejiang Prov Canc Hosp, Zhejiang Canc Res Inst, Zhejiang Canc, Hangzhou, Zhejiang, Peoples R China

[7] Univ Calif San Diego, Dept Pharmacol, Moores Canc Ctr, La Jolla, CA 92093 USA

来源：

ONCOGENE | 2013年 / 32卷 / 05期

关键词：

TET; 5-hydroxymethylation; DNA methylation; cancer biomarker; MAFFUCCI SYNDROME; IDH2; MUTATIONS; OLLIER DISEASE; MAMMALIAN DNA; 5-HYDROXYMETHYLCYTOSINE; 5-CARBOXYLCYTOSINE; CONVERSION; PROTEINS; CANCERS;

D O I：

10.1038/onc.2012.67

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The TET (ten eleven translocation) family of alpha-ketoglutarate (alpha-KG)-dependent dioxygenases catalyzes the sequential oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formyleytosine and 5-carboxylcytosine, leading to eventual DNA demethylation. The TET2 gene is a bona fide tumor suppressor frequently mutated in leukemia, and TET enzyme activity is inhibited in IDH1/2-mutated tumors by the oncometabolite 2-hydroxyglutarate, an antagonist of alpha-KG, linking 5mC oxidation to cancer development. We report here that the levels of 5hmC are dramatically reduced in human breast, liver, lung, pancreatic and prostate cancers when compared with the matched surrounding normal tissues. Associated with the 5hmC decrease is the substantial reduction of the expression of all three TET genes, revealing a possible mechanism for the reduced 5hmC in cancer cells. The decrease of 5hmC was also observed during tumor development in different genetically engineered mouse models. Together, our results identify 5hmC as a biomarker whose decrease is broadly and tightly associated with tumor development. Oncogene (2013) 32, 663-669; doi:10.1038/onc.2012.67;published online 5 March 2012

引用

页码：663 / 669

页数：7

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