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PMID: 22624715 Published · ppublish English Journal Article Meta-Analysis Research Support, N.I.H., Extramural

DNA methylation screening identifies driver epigenetic events of cancer cell survival.

Cancer cell ·Vol. 21 ·No. 5 ·2012-05-15 ·Pages 655-667

De Carvalho DD, Sharma S, You JS, Su SF, Taberlay PC, Kelly TK, Yang X, Liang G, Jones PA

Abstract

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.

MeSH Terms
Cell Death Cell Survival Cell Transformation, Neoplastic/genetics,metabolism,pathology Cluster Analysis Computational Biology DNA Methylation DNA Modification Methylases/genetics,metabolism Epigenesis, Genetic Gene Expression Profiling Gene Expression Regulation, Neoplastic Genetic Predisposition to Disease HCT116 Cells Humans Neoplasms/enzymology,genetics,pathology Phenotype RNA Interference Reproducibility of Results Time Factors Transfection
Chemicals
DNA Modification Methylases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
De Carvalho Daniel D
Department of Urology, Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA.
Sharma Shikhar
Department of Urology, Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA; Program in Genetic, Molecular and Cellular Biology, University of Southern California/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA.
You Jueng Soo
Department of Urology, Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA.
Su Sheng-Fang
Department of Urology, Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA; Program in Genetic, Molecular and Cellular Biology, University of Southern California/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA.
Taberlay Phillippa C
Department of Urology, Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA.
Kelly Theresa K
Department of Urology, Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA.
Yang Xiaojing
Department of Urology, Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA.
Liang Gangning
Department of Urology, Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA.
Jones Peter A
Department of Urology, Biochemistry and Molecular Biology, University of Southern California/Norris Comprehensive Cancer Center Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA. Electronic address: [email protected].
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1878-3686
DOI
10.1016/j.ccr.2012.03.045
Email
[email protected]
Published
2012-05-15
Pages
655-667
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC3395886
Subset
IM
Grants
NCI NIH HHS · R01 CA170550 · United States
NCI NIH HHS · R37 CA082422 · United States
NCI NIH HHS · R37CA082422 · United States
Databases
GEO
GSE36534
Corrections
CommentIn
PMID: 22673152
External Links
PubMed source DOI: 10.1016/j.ccr.2012.03.045 PMC Full Text View journal details
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