Molecular genetic analysis of ependymal tumors - NF2 mutations and chromosome 22q loss occur preferentially in intramedullary spinal ependymomas
Molecular genetic analysis of ependymal tumors - NF2 mutations and chromosome 22q loss occur preferentially in intramedullary spinal ependymomas
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DOI：
10.1016/s0002-9440(10)65158-9
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发表时间：
1999-08-01
影响因子：
6
通讯作者：
von Deimling, A
中科院分区：
文献类型：
--
作者：
Ebert, C;von Haken, M;von Deimling, A
室管膜肿瘤在形态、定位、首次临床表现的年龄和预后方面具有异质性。据报道，这些肿瘤中存在一些分子改变，包括染色体10、17和22上的等位基因丢失和NF2基因突变。然而，与星形细胞胶质瘤相反，不同类型的室管膜肿瘤没有一致的分子改变。为了评估室管膜瘤的形态亚群是否以特定的遗传病变为特征，我们分析了一系列62例室管膜肿瘤，包括黏液乳头状室管膜瘤、室管膜下瘤、室管膜瘤和间变性室管膜瘤，分析了染色体臂10q和22q上的等位基因缺失以及PTEN和NF2基因的突变。56例肿瘤中有5例和54例肿瘤中有12例分别检测到10q和22q等位基因缺失。6例室管膜瘤携带体细胞NF2突变，而PTEN基因未检测到突变。这些发现表明，相当一部分的脊髓室管膜瘤与涉及22号染色体的分子事件有关，NF2基因的突变可能是其发生的主要原因。此外，我们的数据表明，脊柱室管膜瘤更有利的临床病程可能与不同于脑内室管膜瘤的独特遗传改变模式有关。
Ependymal tumors are heterogeneous with regard to morphology, localization, age at first clinical manifestation, and prognosis. Several molecular alterations have been reported in these tumors, including allelic losses on chromosomes 10, 17, and 22 and mutations in the NF2 gene. However, in contrast to astrocytic gliomas, no consistent molecular alterations have been associated with distinct types of ependymal tumors. To evaluate whether morphological subsets of ependymomas are characterized by specific genetic lesions, we analyzed a series of 62 ependymal tumors, including myxopapillary ependymomas, subependymomas, ependymomas, and anaplastic ependymomas, for allelic losses on chromosome arms 10q and 22q and mutations in the PTEN and NF2 genes. Allelic losses on 10q and 22q were detected In 5 of 56 and 12 of 54 tumors, respectively. Six ependymomas carried somatic NF2 mutations, whereas no mutations were detected in the]PTEN gene. AU six of the NF2 mutations occurred in ependymomas of WHO grade II and were exclusively observed in tumors with a spinal localization (P = 0.0063), These findings suggest that a considerable fraction of spinal ependymomas are associated with molecular events involving chromosome 22 and that mutations in the NF2 gene may be of primary importance for their genesis. Furthermore, our data suggest that the more favorable clinical course of spinal ependymomas may relate to a distinct pattern of genetic alterations different from that of intracerebral ependymomas.