Epigenetic dysregulation of<i>TET2</i>in human glioblastoma

Abstract

// Mar&iacute;a G. Garc&iacute;a 1, 2 , Antonella Carella 1, 2 , Roc&iacute;o G. Urdinguio 2 , Gustavo F. Bay&oacute;n 1 , Virginia Lopez 2 , Juan Ram&oacute;n Tejedor 1, 3 , Marta I. Sierra 1 , Estela Garc&iacute;a-Tora&ntilde;o 1 , Pablo Santamarina 1 , Ra&uacute;l F. Perez 1 , Cristina Mangas 1 , Aurora Astudillo 4 , M. Daniela Corte-Torres 5 , In&eacute;s S&aacute;enz-de-Santa-Mar&iacute;a 6 , Mar&iacute;a-Dolores Chiara 6 , Agust&iacute;n F. Fern&aacute;ndez 1, 3 and Mario F. Fraga 2 1 Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, Spain 2 Nanomaterials and Nanotechnology Research Center (CINN-CSIC), Universidad de Oviedo, El Entrego, Asturias, Spain 3 Fundaci&oacute;n para la Investigaci&oacute;n Biosanitaria de Asturias (FINBA), Instituto de Investigaci&oacute;n Sanitaria del Principado de Asturias (ISPA), Oviedo, Asturias, Spain 4 Department of Pathology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain 5 Biobanco del Principado de Asturias, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain 6 Otorhinolaryngology Service, Hospital Universitario Central de Asturias, Instituto Universitario de Oncolog&iacute;a del Principado de Asturias, Universidad de Oviedo, CIBERONC, Oviedo, Spain Correspondence to: Mario F. Fraga, email: mffraga@cinn.es Agust&iacute;n F. Fern&aacute;ndez, email: affernandez@hca.es Keywords: 5-hydroxymehtylcytosine; glioblastoma; TET2; epigenetics; DNA methylation Received: September 08, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: April 28, 2018&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; 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.