Chromosomal and genetic abnormalities in ependymomas detected by fluorescence in situ hybridization or microarray assay

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Ependymomas account for approximately 3-5% of central nervous system (CNS) tumors. These entities have not yet been subjected to systematic chromosomal and genetic studies. We conducted immunohistochemistry, fluorescence in situ hybridization (FISH) analysis and microarray assay on 37 ependymomas and examined the correlation of chromosomal abnormalities with clinicopathological findings. Paraffin-embedded surgical specimens for 22 intracranial and 15 spinal ependymoma cases were obtained from Saitama Medical School Hospital and its collaborating hospitals (Tokyo Univ., Hiroshima Univ., Hokkaido Univ., Kyorin Univ., Dokkyo University School of Medicine, Otsu Municipal Hospital and Showa General Hospital) in Japan. Human bacterial artificial chromosome (BAC) clones specific to each chromosomal locus were used as FISH probes. BAG DNA was labeled using the Nick Translation method. Eleven (50%) of 22 grade II ependymomas had increased numbers of chromosome 5, regardless of localization of the tumors. Deletions at chromosome 22q12.2 (within the NF2 gene) were found in 3 (13.6%) of 22 intracranial and 8 (53.3%) of 15 spinal ependymomas. Deletions at chromosome 17p13.3 were detected in none of 23 grade II ependymomas and 6 (40%) of 15 anaplastic ependymomas. The incidence of chromosome 17p13.3 loss in anaplastic ependymomas was significantly higher than that in grade II ependymomas (p < 0.01). These results suggest that chromosome 5 aberrations and alteration of the NF2 gene are involved in a subset of grade II ependymomas and spinal ependymomas, respectively. It is possible that chromosome 17p13.3 loss occurs late in the progression of ependymomas and/or causes phenotypic changes of ependymoma cells into more aggressive ones.