title: Cancer-related epigenome changes associated with reprogramming to induced pluripotent stem cells.
abstract: 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.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Ohm
authors.forename: Prashant
authors.initials: P
authors.lastname: Mali
authors.forename: Leander
authors.initials: L
authors.lastname: Van Neste
authors.forename: David M
authors.initials: DM
authors.lastname: Berman
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.forename: Kurinji
authors.initials: K
authors.lastname: Pandiyan
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Briggs
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Pedram
authors.initials: P
authors.lastname: Argani
authors.forename: Brian
authors.initials: B
authors.lastname: Simons
authors.forename: Wayne
authors.initials: W
authors.lastname: Yu
authors.forename: William
authors.initials: W
authors.lastname: Matsui
authors.forename: Wim
authors.initials: W
authors.lastname: Van Criekinge
authors.forename: Feyruz V
authors.initials: FV
authors.lastname: Rassool
authors.forename: Elias
authors.initials: E
authors.lastname: Zambidis
authors.forename: Kornel E
authors.initials: KE
authors.lastname: Schuebel
authors.forename: Leslie
authors.initials: L
authors.lastname: Cope
authors.forename: Jonathan
authors.initials: J
authors.lastname: Yen
authors.forename: Helai P
authors.initials: HP
authors.lastname: Mohammad
authors.forename: Linzhao
authors.initials: L
authors.lastname: Cheng
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Baylin
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002843:Chromatin / Q000235:genetics; D019175:DNA Methylation; D005347:Fibroblasts / Q000502:physiology; D020869:Gene Expression Profiling; D020868:Gene Silencing; D015894:Genome, Human; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D039904:Pluripotent Stem Cells / Q000473:pathology / Q000502:physiology*
chemical_list: D002843:Chromatin