title: Aberrant CpG island methylation of multiple genes in ependymal tumors.
abstract: Aberrant methylation of promoter CpG islands in human genes represents an alternative mechanism for genetic inactivation, and contributes to the development of human tumors. Nevertheless, thus far, few reports have analyzed methylation in ependymomas. We determined the frequency of aberrant CpG island methylation of several tumor-associated genes: p16(INK4a), RB1, MGMT, DAPK, TIMP3, THBS1, TP73, NF2 and Caspase 8 in a group of 27 ependymomas, consisting of 22 WHO grade II samples and five anaplastic WHO grade III tumors. The respective methylation indices (number of genes methylated/total genes analyzed) for both tumor groups was 0.195 and 0.198. Overall methylation rates greater than 20% were detected in MGMT, TIMP3, THBS1 and TP73. NF2 and Caspase 8 each presented hypermethylation in less than 10% of cases, and the cell-cycle regulators RB1/p16(INK4a) were hypermethylated in 4% and 18% of the samples, respectively, mostly affecting the low-grade forms. Our findings suggest that methylation commonly contributes to the inactivation of cancer-related genes in ependymomas.
authors.affiliation: Laboratorio de Oncogenetica Molecular, Dept. C. Experimental, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: M Eva
authors.initials: ME
authors.lastname: Alonso
authors.forename: M Josefa
authors.initials: MJ
authors.lastname: Bello
authors.forename: Pilar
authors.initials: P
authors.lastname: Gonzalez-Gomez
authors.forename: Dolores
authors.initials: D
authors.lastname: Arjona
authors.forename: Jose M
authors.initials: JM
authors.lastname: de Campos
authors.forename: Manuel
authors.initials: M
authors.lastname: Gutierrez
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rey
mesh_terms: D000293:Adolescent; D000328:Adult; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004806:Ependymoma / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction