Bian Liu-Guan, Tirakotai Wuttipong, Sun Qing-Fang, Zhao Wei-Guo, Shen Jian-Kang, Luo Qi-Zhong
Department of Neurosurgery, Rui-Jin Hospital, Shanghai Second Medical University, Shanghai, The People's Republic of China.
J Neurooncol. 2005 Jul;73(3):253-60. doi: 10.1007/s11060-004-5176-3.
To analyze the molecular genetic alteration of sporadic vestibular schwannomas from the People's Republic of China and to correlate these alterations with the tumor behaviors.
Four highly polymorphic microsatellite DNA markers were used to observe the frequency of loss of heterozygosity (LOH) in chromosome 22. The NF2 gene mutations were detected by Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and DNA sequencing. The schwannomin/merlin (S/M) expression was examined using anti-NF2 (A-19) IgG under immunohistochemistry and western blot. The proliferative index (LI) of vestibular schwannoma was evaluated by proliferative cell nuclear antigen investigation.
Sixteen vestibular schwannomas (44.4%) showed allele loss. We found 22 mutations in 36 schwannomas. The LI and the growth rate of schwannomas with LOH or mutation were significantly higher than those without LOH or mutation. All of these vestibular schwannomas showed no immunoreaction to anti-NF2(A-19) IgG by immunohistochemistry. By immunoblotting technique, reduced expression of S/M was found in 31 cases (86%). The growth index of schwannomas with severely reduced expression of S/M was significantly higher than those with moderately reduced or normal expression.
The molecular genetic changes in sporadic vestibular schwannomas from Chinese patients were similar to the previous reports. We demonstrate the relationship between tumor behaviors and genetic alteration (including LOH and mutation of NF2 gene). We propose that inactivation of S/M, may be an important step in tumorigenesis of sporadic vestibular schwannoma.
分析来自中华人民共和国的散发性前庭神经鞘瘤的分子遗传学改变，并将这些改变与肿瘤行为相关联。
使用四个高度多态性的微卫星DNA标记观察22号染色体杂合性缺失（LOH）的频率。通过聚合酶链反应-单链构象多态性（PCR-SSCP）和DNA测序检测NF2基因突变。在免疫组织化学和蛋白质印迹法下，使用抗NF2（A-19）IgG检测施万蛋白/默林（S/M）的表达。通过增殖细胞核抗原检测评估前庭神经鞘瘤的增殖指数（LI）。
16例前庭神经鞘瘤（44.4%）显示等位基因缺失。我们在36例神经鞘瘤中发现了22个突变。具有LOH或突变的神经鞘瘤的LI和生长速率显著高于没有LOH或突变的神经鞘瘤。所有这些前庭神经鞘瘤在免疫组织化学中对抗NF2（A-19）IgG均无免疫反应。通过免疫印迹技术，在31例（86%）中发现S/M表达降低。S/M表达严重降低的神经鞘瘤的生长指数显著高于S/M表达中度降低或正常的神经鞘瘤。
中国患者散发性前庭神经鞘瘤的分子遗传学变化与先前报道相似。我们证明了肿瘤行为与基因改变（包括NF2基因的LOH和突变）之间的关系。我们提出，S/M的失活可能是散发性前庭神经鞘瘤肿瘤发生的重要步骤。
