Research Papers:
Epigenetic dysregulation of TET2 in human glioblastoma
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Abstract
María G. García1,2, Antonella Carella1,2, Rocío G. Urdinguio2, Gustavo F. Bayón1, Virginia Lopez2, Juan Ramón Tejedor1,3, Marta I. Sierra1, Estela García-Toraño1, Pablo Santamarina1, Raúl F. Perez1, Cristina Mangas1, Aurora Astudillo4, M. Daniela Corte-Torres5, Inés Sáenz-de-Santa-María6, María-Dolores Chiara6, Agustín F. Fernández1,3 and Mario F. Fraga2
1Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain
2Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Universidad de Oviedo, El Entrego, Asturias, Spain
3Fundación para la Investigación Biosanitaria de Asturias (FINBA), Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain
4Department of Pathology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
5Biobanco del Principado de Asturias, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain
6Otorhinolaryngology Service, Hospital Universitario Central de Asturias, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, CIBERONC, Oviedo, Spain
Correspondence to:
Mario F. Fraga, email: [email protected]
Agustín F. Fernández, email: [email protected]
Keywords: 5-hydroxymehtylcytosine; glioblastoma; TET2; epigenetics; DNA methylation
Received: September 08, 2017 Accepted: April 28, 2018 Published: May 25, 2018
ABSTRACT
Ten-eleven translocation (TET) enzymes are frequently deregulated in cancer, but the underlying molecular mechanisms are still poorly understood. Here we report that TET2 shows frequent epigenetic alterations in human glioblastoma including DNA hypermethylation and hypo-hydroxymethylation, as well as loss of histone acetylation. Ectopic overexpression of TET2 regulated neural differentiation in glioblastoma cell lines and impaired tumor growth. Our results suggest that epigenetic dysregulation of TET2 plays a role in human glioblastoma.
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