Table of Contents
ISRN Neurology
Volume 2012 (2012), Article ID 576578, 10 pages
http://dx.doi.org/10.5402/2012/576578
Research Article

Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas

1Unidad de Biología de Tumores Cerebrales, Universidad de Navarra, 31008 Pamplona, Spain
2Gene Expression and Cancer Group, Vall d’Hebrón Instituto de Oncología, 08035 Barcelona, Spain
3Departamento de Ciencias de la Salud, Universidad Pública de Navarra, 31008 Pamplona, Spain
4Servicio de Neurocirugía, Hospital de Navarra, 31008 Pamplona, Spain
5Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
6Servicio de Anatomía Patológica, Hospital Miguel Servet, 50009 Zaragoza, Spain
7Servicio de Anatomía Patológica, Hospital de Navarra, 31008 Pamplona, Spain
8Unidad de Investigación IdiPAZ, Hospital Universitario La Paz, 28046 Madrid, Spain

Received 25 August 2011; Accepted 29 September 2011

Academic Editor: C.-M. Chen

Copyright © 2012 Jorge Muñoz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

While allelic losses and mutations of tumor suppressor genes implicated in the etiology of astrocytoma have been widely assessed, the role of epigenetics is still a matter of study. We analyzed the frequency of promoter hypermethylation by methylation-specific PCR (MSP) in five tumor suppressor genes (PTEN, MGMT, RASSF1A, p14ARF, and p16INK4A), in astrocytoma samples and cell lines. RASSF1A was the most frequently hypermethylated gene in all grades of astrocytoma samples, in cell lines, and in adult secondary GBM. It was followed by MGMT. PTEN showed a slight methylation signal in only one GBM and one pilocytic astrocytoma, and in two cell lines; while p14ARF and p16INK4A did not show any evidence of methylation in primary tumors or cell lines. In pediatric GBM, RASSF1A was again the most frequently altered gene, followed by MGMT; PTEN, p14 and p16 showed no alterations. Lack or reduced expression of RASSF1A in cell lines was correlated with the presence of methylation. RASSF1A promoter hypermethylation might be used as a diagnostic marker for secondary GBM and pediatric GBM. Promoter hypermethylation might not be an important inactivation mechanism in other genes like PTEN, p14ARF and p16INK4A, in which other alterations (mutations, homozygous deletions) are prevalent.