Analysis of HIC-1 methylation and transcription in human ependymomas

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.