title: Analysis of HIC-1 methylation and transcription in human ependymomas.
abstract: Ependymomas are among the most common brain tumors in children. They develop from ependymal cells lining the ventricular system of the CNS. Previous studies have demonstrated a significant rate of allelic loss at chromosome 17p13.3. The HIC-1 putative tumor-suppressor gene, which exhibits hypermethylation and loss of expression in various tumor entities including medulloblastomas and gliomas, maps to the affected region. In the present study, we analyzed HIC-1 in ependymomas. Therefore, we applied methylation-specific PCR of the 5'-untranslated region as well as of a central region of HIC-1 and bisulfite sequencing to determine the methylation status in 52 ependymomas of different histologic subtypes, grades and locations. In addition, we used a competitive RT-PCR approach for sensitive assessment of HIC-1 transcripts. Hypermethylation of at least one of the 2 analyzed regions was found in 43/52 (83%) cases. There was a significant correlation between hypermethylation of HIC-1 and nonspinal localization (p = 0.019) as well as age. Of 27 ependymomas, 22 (81%) showed absent or low expression of HIC-1. The elevated methylation of HIC-1 in nonspinal ependymomas supports the hypothesis that spinal and nonspinal ependymomas represent genetically distinct entities.
authors.affiliation: Department of Neuropathology, University of Bonn, Bonn, Germany. awaha1@uni-bonn.de
authors.forename: Anke
authors.initials: A
authors.lastname: Waha
authors.forename: Arend
authors.initials: A
authors.lastname: Koch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hartmann
authors.forename: Heike
authors.initials: H
authors.lastname: Mack
authors.forename: Johannes
authors.initials: J
authors.lastname: Schramm
authors.forename: Niels
authors.initials: N
authors.lastname: Sörensen
authors.forename: Frank
authors.initials: F
authors.lastname: Berthold
authors.forename: Otmar D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Andreas
authors.initials: A
authors.lastname: Waha
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D004806:Ependymoma / Q000235:genetics*; D005260:Female; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: C096870:Hic1 protein, mouse; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors