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

室管膜瘤约占中枢神经系统（CNS）肿瘤的3-5%。这些实体尚未进行系统的染色体和遗传研究。我们对37例室管膜瘤进行了免疫组织化学、荧光原位杂交（FISH）和微阵列分析，并检查了染色体异常与临床病理结果的相关性。石蜡包埋手术标本来自日本埼玉医学院医院及其合作医院（东京大学、广岛大学、北海道大学、高丽大学、Dokkyo大学医学院、大津市立医院和昭和总医院）22例颅内和15例脊髓室管膜瘤。每个染色体位点特异性的人细菌人工染色体（BAC）克隆作为FISH探针。采用Nick翻译法对BAG DNA进行标记。22例II级室管膜瘤中有11例（50%）的5号染色体数目增加，与肿瘤的位置无关。22例颅内瘤中有3例（13.6%）和15例脊髓室管膜瘤中有8例（53.3%）存在22q12.2染色体缺失（NF2基因内）。23例II级室管膜瘤中未发现染色体17p13.3缺失，15例间变性室管膜瘤中有6例（40%）检测到染色体17p13.3缺失。间变性室管膜瘤中染色体17p13.3缺失的发生率明显高于II级室管膜瘤（p < 0.01）。这些结果表明，5号染色体畸变和NF2基因的改变分别与II级室管膜瘤和脊髓室管膜瘤有关。染色体17p13.3缺失可能发生在室管膜瘤进展的晚期，并且/或者导致室管膜瘤细胞表型改变为更具侵袭性的细胞。

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.