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Is Glioblastoma an Epigenetic Malignancy?
Laboratory of Molecular Neurobiology, Neurobiology Center, The Nencki Institute of Experimental Biology, 3 Pasteur Str., Warsaw 02-093, Poland
* Author to whom correspondence should be addressed.
Received: 15 July 2013; in revised form: 13 August 2013 / Accepted: 19 August 2013 / Published: 3 September 2013
Abstract: Epigenetic modifications control gene expression by regulating the access of nuclear proteins to their target DNA and have been implicated in both normal cell differentiation and oncogenic transformation. Epigenetic abnormalities can occur both as a cause and as a consequence of cancer. Oncogenic transformation can deeply alter the epigenetic information enclosed in the pattern of DNA methylation or histone modifications. In addition, in some cancers epigenetic dysfunctions can drive oncogenic transformation. Growing evidence emphasizes the interplay between metabolic disturbances, epigenomic changes and cancer, i.e., mutations in the metabolic enzymes SDH, FH, and IDH may contribute to cancer development. Epigenetic-based mechanisms are reversible and the possibility of “resetting” the abnormal cancer epigenome by applying pharmacological or genetic strategies is an attractive, novel approach. Gliomas are incurable with all current therapeutic approaches and new strategies are urgently needed. Increasing evidence suggests the role of epigenetic events in development and/or progression of gliomas. In this review, we summarize current data on the occurrence and significance of mutations in the epigenetic and metabolic enzymes in pathobiology of gliomas. We discuss emerging therapies targeting specific epigenetic modifications or chromatin modifying enzymes either alone or in combination with other treatment regimens.
Keywords: epigenetics; methylator phenotype; histone modifying enzymes; inhibitors and glioblastoma
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Maleszewska, M.; Kaminska, B. Is Glioblastoma an Epigenetic Malignancy? Cancers 2013, 5, 1120-1139.
Maleszewska M, Kaminska B. Is Glioblastoma an Epigenetic Malignancy? Cancers. 2013; 5(3):1120-1139.
Maleszewska, Marta; Kaminska, Bozena. 2013. "Is Glioblastoma an Epigenetic Malignancy?" Cancers 5, no. 3: 1120-1139.