Oncotarget

Research Papers:

Epigenetic dysregulation of TET2 in human glioblastoma

María G. García, Antonella Carella, Rocío G. Urdinguio, Gustavo F. Bayón, Virginia Lopez, Juan Ramón Tejedor, Marta I. Sierra, Estela García-Toraño, Pablo Santamarina, Raúl F. Perez, Cristina Mangas, Aurora Astudillo, M. Daniela Corte-Torres, Inés Sáenz-de-Santa-María, María-Dolores Chiara, Agustín F. Fernández and Mario F. Fraga _

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Oncotarget. 2018; 9:25922-25934. https://doi.org/10.18632/oncotarget.25406

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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: 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.


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