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Epigenetic dysregulation of TET2 in human glioblastoma

2018; Impact Journals LLC; Volume: 9; Issue: 40 Linguagem: Inglês

10.18632/oncotarget.25406

1949-2553

María González García, Antonella Carella, Rocío G. Urdinguio, Gustavo F. Bayón, Virginia López, Juan Ramón Tejedor, Marta Sierra, Estela García‐Toraño, Pablo Santamarina‐Ojeda, Raúl F. Pérez, Cristina Mangas, Aurora Astudillo, María D. Corte‐Torres, Inés Sáenz‐de‐Santa‐María, María‐Dolores Chiara, Agustín F. Fernández, Mario F. Fraga,

Genomics and Chromatin Dynamics

// María G. García 1, 2 , Antonella Carella 1, 2 , Rocío G. Urdinguio 2 , Gustavo F. Bayón 1 , Virginia Lopez 2 , Juan Ramón Tejedor 1, 3 , Marta I. Sierra 1 , Estela García-Toraño 1 , Pablo Santamarina 1 , Raúl F. Perez 1 , Cristina Mangas 1 , Aurora Astudillo 4 , M. Daniela Corte-Torres 5 , Inés Sáenz-de-Santa-María 6 , María-Dolores Chiara 6 , Agustín F. Fernández 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 Fundación para la Investigación Biosanitaria de Asturias (FINBA), Instituto de Investigación 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 Oncología del Principado de Asturias, Universidad de Oviedo, CIBERONC, Oviedo, Spain Correspondence to: Mario F. Fraga, email: mffraga@cinn.es Agustín F. Fernández, email: affernandez@hca.es 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.