DNA Methylation Screening Identifies Driver Epigenetic Events of Cancer Cell Survival

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 methyl...

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Bibliographic Details
Published in:Cancer cell 2012-05, Vol.21 (5), p.655-667
Main Authors: De Carvalho, Daniel D., Sharma, Shikhar, You, Jueng Soo, Su, Sheng-Fang, Taberlay, Phillippa C., Kelly, Theresa K., Yang, Xiaojing, Liang, Gangning, Jones, Peter A.
Format: Article
Language:English
Subjects:
Cell Death
Cell Survival
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Cell Transformation, Neoplastic - pathology
Cluster Analysis
Computational Biology
DNA Methylation
DNA Modification Methylases - genetics
DNA Modification Methylases - metabolism
Epigenesis, Genetic
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
HCT116 Cells
Humans
Neoplasms - enzymology
Neoplasms - genetics
Neoplasms - pathology
Phenotype
Reproducibility of Results
RNA Interference
Time Factors
Transfection
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Summary: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. ► An approach to discriminate between “driver” and “passenger” epigenetic events ► Cancer cells become dependent on DNA methylation of a few key target genes ► Somatic cells depend on DNA methylation to silence some germline-specific genes ► Cells in culture rely on aberrant DNA methylation for survival
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2012.03.045