DNA Methylation Screening Identifies Driver Epigenetic Events of Cancer Cell Survival

被引：224

作者：

De Carvalho, Daniel D. ^{[1
]}

Sharma, Shikhar ^{[1
,2
]}

You, Jueng Soo ^{[1
]}

Su, Sheng-Fang ^{[1
,2
]}

Taberlay, Phillippa C. ^{[1
]}

Kelly, Theresa K. ^{[1
]}

Yang, Xiaojing ^{[1
]}

Liang, Gangning ^{[1
]}

Jones, Peter A. ^{[1
]}

机构：

[1] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Urol Biochem & Mol Biol, Los Angeles, CA 90089 USA

[2] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Program Genet Mol & Cellular Biol, Los Angeles, CA 90089 USA

来源：

CANCER CELL | 2012年 / 21卷 / 05期

关键词：

TUMOR-SUPPRESSOR GENES; DE-NOVO METHYLATION; CPG ISLAND; P53; RESTORATION; UP-REGULATION; IRAK-M; HYPERMETHYLATION; PATTERNS; DNMT1; ACTIVATION;

D O I：

10.1016/j.ccr.2012.03.045

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Cancer cells typically exhibit aberrant DNA methylation patterns that can drive malignant transformation. Whether cancer cells are dependent on these abnormal epigenetic modifications remains elusive. We used experimental and bioinformatic approaches to unveil genomic regions that require DNA methylation for survival of cancer cells. First, we surveyed the residual DNA methylation profiles in cancer cells with highly impaired DNA methyltransferases. Then, we clustered these profiles according to their DNA methylation status in primary normal and tumor tissues. Finally, we used gene expression meta-analysis to identify regions that are dependent on DNA methylation-mediated gene silencing. We further showed experimentally that these genes must be silenced by DNA methylation for cancer cell survival, suggesting these are key epigenetic events associated with tumorigenesis.

引用

页码：655 / 667

页数：13

共 59 条

[1] HIGH-LEVELS OF DENOVO METHYLATION AND ALTERED CHROMATIN STRUCTURE AT CPG ISLANDS IN CELL-LINES [J].