title: DNA methylation screening identifies driver epigenetic events of cancer cell survival.
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.
authors.affiliation: 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.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: De Carvalho
authors.affiliation: 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.
authors.forename: Shikhar
authors.initials: S
authors.lastname: Sharma
authors.affiliation: 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.
authors.forename: Jueng Soo
authors.initials: JS
authors.lastname: You
authors.affiliation: 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.
authors.forename: Sheng-Fang
authors.initials: SF
authors.lastname: Su
authors.affiliation: 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.
authors.forename: Phillippa C
authors.initials: PC
authors.lastname: Taberlay
authors.affiliation: 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.
authors.forename: Theresa K
authors.initials: TK
authors.lastname: Kelly
authors.affiliation: 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.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Gangning
authors.initials: G
authors.lastname: Liang
authors.affiliation: 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: pjones@med.usc.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Jones
mesh_terms: D016923:Cell Death; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016000:Cluster Analysis; D019295:Computational Biology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D045325:HCT116 Cells; D006801:Humans; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D015203:Reproducibility of Results; D013997:Time Factors; D014162:Transfection
chemical_list: D015254:DNA Modification Methylases