title: Concise review: dedifferentiation meets cancer development: proof of concept for epigenetic cancer.
abstract: The technology for generation of induced pluripotent stem cells (iPSCs) has made significant contributions to various scientific fields, and the field of cancer biology is no exception. Although cancer is generally believed to develop through accumulation of multiple genetic mutations, there is increasing evidence that cancer cells also acquire epigenetic abnormalities during development, maintenance, and progression. Because the epigenetic status of somatic cells changes dynamically through reprogramming, iPSC technology can be utilized to actively and globally alter the epigenetic status of differentiated cells. Using this technology, a recent study has revealed that some types of cancer can develop mainly through disruption of the epigenetic status triggered by dedifferentiation. In this paper, we outline the reprograming process and the epigenetic mechanism associated with the maintenance or conversion of cell identity. We then describe several observations suggesting that dedifferentiation can play an important role in cancer development. Finally, we introduce the system responsible for in vivo reprogramming to demonstrate the involvement of dedifferentiation-driven epigenetic disruption in cancer development, and propose that particular types of cancer can develop predominantly through epigenetic alterations.
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan; Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan; Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Haga
authors.affiliation: Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan; Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan y-yamada@cira.kyoto-u.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation / Q000235:genetics*; D065150:Cellular Reprogramming / Q000235:genetics; D044127:Epigenesis, Genetic / Q000502:physiology*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000502:physiology; D009369:Neoplasms / Q000235:genetics*
keywords: Dedifferentiation; Epigenetic cancer; In vivo reprogramming; Induced pluripotent stem cells; Wilms’ tumor