Cancer-Related Epigenome Changes Associated with Reprogramming to Induced Pluripotent Stem Cells

被引：56

作者：

Ohm, Joyce E. ^{[1
]}

Mali, Prashant ^{[5
]}

Van Neste, Leander ^{[9
,10
]}

Berman, David M. ^{[7
]}

Liang, Liang ^{[1
]}

Pandiyan, Kurinji ^{[1
,2
]}

Briggs, Kimberly J. ^{[2
]}

Zhang, Wei ^{[1
]}

Argani, Pedram ^{[7
]}

Simons, Brian

Yu, Wayne ^{[1
]}

Matsui, William ^{[1
]}

Van Criekinge, Wim ^{[9
,10
]}

Rassool, Feyruz V. ^{[8
]}

Zambidis, Elias ^{[6
]}

Schuebel, Kornel E. ^{[1
]}

Cope, Leslie

Yen, Jonathan ^{[5
]}

Mohammad, Helai P. ^{[1
]}

Cheng, Linzhao ^{[2
,3
,4
]}

Baylin, Stephen B. ^{[1
,2
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA

[2] Johns Hopkins Univ, Sch Med, Program Cellular & Mol Med, Baltimore, MD 21231 USA

[3] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21231 USA

[4] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21231 USA

[5] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21231 USA

[6] Johns Hopkins Univ, Sch Med, Dept Pediat Oncol, Baltimore, MD 21231 USA

[7] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA

[8] Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA

[9] Univ Ghent, Fac Biosci Engn, Dept Mol Biotechnol, B-9000 Ghent, Belgium

[10] OncoMethylome Sci SA, Liege, Belgium

来源：

CANCER RESEARCH | 2010年 / 70卷 / 19期

关键词：

TUMOR-SUPPRESSOR GENES; DNA METHYLATION; DEVELOPMENTAL REGULATORS; CHROMATIN PATTERN; INDUCTION; POLYCOMB; FIBROBLASTS; COMPLEXES; ADULT; DNMT1;

D O I：

10.1158/0008-5472.CAN-10-1361

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The ability to induce pluripotent stem cells from committed, somatic human cells provides tremendous potential for regenerative medicine. However, there is a defined neoplastic potential inherent to such reprogramming that must be understood and may provide a model for understanding key events in tumorigenesis. Using genome-wide assays, we identify cancer-related epigenetic abnormalities that arise early during reprogramming and persist in induced pluripotent stem cell (iPS) clones. These include hundreds of abnormal gene silencing events, patterns of aberrant responses to epigenetic-modifying drugs resembling those for cancer cells, and presence in iPS and partially reprogrammed cells of cancer-specific gene promoter DNA methylation alterations. Our findings suggest that by studying the process of induced reprogramming, we may gain significant insight into the origins of epigenetic gene silencing associated with human tumorigenesis, and add to means of assessing iPS for safety. Cancer Res; 70(19); 7662-73. (C) 2010 AACR.

引用

页码：7662 / 7673

页数：12

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