von Deimling A, Kraus J A, Stangl A P, Wellenreuther R, Lenartz D, Schramm J, Louis D N, Ramesh V, Gusella J F, Wiestler O D
Department of Neuropathology, University of Bonn Medical Center, Germany.
Brain Pathol. 1995 Jan;5(1):11-4. doi: 10.1111/j.1750-3639.1995.tb00571.x.
Meningiomas are among the most common human brain tumors. Occasionally patients develop multiple meningiomas. While it has been surmised that these are multiple primary meningiomas, it is possible that they represent spread of a single primary tumor. Recently, the neurofibromatosis type 2 (NF2) tumor suppressor gene has been shown to carry mutations in meningiomas. In the present study we have analyzed multiple meningiomas from two patients for point mutations in the NF2 gene by SSCP analysis and direct sequencing. We detected point mutations in the meningiomas from both patients. The first patient from which six tumors were available had a three base pair deletion in the splice donor region of exon 7. All tumors showed the identical mutation. The second patient with two independent meningiomas had a nonsense mutation in exon 8 which was the same in both tumors. Analysis of constitutional DNA revealed a wildtype DNA sequence in both cases. There was no family history of neurofibromatosis type 2 in either patient. These data provide strong evidence for a monoclonal origin of multiple meningiomas. Early subarachnoid spread is the most likely mechanism for the formation of these tumors.
脑膜瘤是人类最常见的脑肿瘤之一。偶尔，患者会发生多发性脑膜瘤。虽然推测这些是多发性原发性脑膜瘤，但它们也有可能是单一原发性肿瘤的扩散。最近，已证明2型神经纤维瘤病（NF2）肿瘤抑制基因在脑膜瘤中存在突变。在本研究中，我们通过单链构象多态性分析（SSCP）和直接测序，分析了两名患者的多发性脑膜瘤中NF2基因的点突变。我们在两名患者的脑膜瘤中均检测到点突变。第一名患者有六个肿瘤，其7号外显子的剪接供体区域有一个三碱基对缺失。所有肿瘤均显示相同的突变。第二名患有两个独立脑膜瘤的患者，其8号外显子有一个无义突变，两个肿瘤中的该突变相同。对其基因组DNA的分析显示，两例患者的DNA序列均为野生型。两名患者均无2型神经纤维瘤病家族史。这些数据为多发性脑膜瘤的单克隆起源提供了有力证据。早期蛛网膜下腔播散是这些肿瘤形成的最可能机制。
