Ebert C, von Haken M, Meyer-Puttlitz B, Wiestler O D, Reifenberger G, Pietsch T, von Deimling A
Department of Neuropathology, University of Bonn Medical Center, Bonn Charité, Humboldt University, Berlin, Germany.
Am J Pathol. 1999 Aug;155(2):627-32. doi: 10.1016/S0002-9440(10)65158-9.
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. All 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.
室管膜瘤在形态、定位、首次临床表现时的年龄以及预后方面具有异质性。这些肿瘤中已报道了几种分子改变，包括染色体10、17和22上的等位基因缺失以及NF2基因的突变。然而，与星形胶质细胞瘤不同，没有一致的分子改变与不同类型的室管膜瘤相关。为了评估室管膜瘤的形态学亚组是否具有特定的基因损伤特征，我们分析了一系列62例室管膜瘤，包括黏液乳头型室管膜瘤、室管膜下瘤、室管膜瘤和间变性室管膜瘤，检测其10q和22q染色体臂上的等位基因缺失以及PTEN和NF2基因的突变。分别在56例肿瘤中的5例和54例肿瘤中的12例中检测到10q和22q上的等位基因缺失。6例室管膜瘤携带体细胞NF2突变，而在PTEN基因中未检测到突变。所有6例NF2突变均发生在世界卫生组织II级室管膜瘤中，且仅在脊髓定位的肿瘤中观察到（P = 0.0063）。这些发现表明，相当一部分脊髓室管膜瘤与涉及染色体22的分子事件相关，并且NF2基因的突变可能对其发生至关重要。此外，我们的数据表明，脊髓室管膜瘤更有利的临床病程可能与不同于脑室内室管膜瘤的独特基因改变模式有关。
