Lekanne Deprez R H, Bianchi A B, Groen N A, Seizinger B R, Hagemeijer A, van Drunen E, Bootsma D, Koper J W, Avezaat C J, Kley N
Department of Pathology, Erasmus University, Rotterdam, The Netherlands.
Am J Hum Genet. 1994 Jun;54(6):1022-9.
The gene for the hereditary disorder neurofibromatosis type 2 (NF2), which predisposes for benign CNS tumors such as vestibular schwannomas and meningiomas, has been assigned to chromosome 22 and recently has been isolated. Mutations in the NF2 gene were found in both sporadic meningiomas and vestibular schwannomas. However, so far only 6 of the 16 exons of the gene have been analyzed. In order to extend the analysis of an involvement of the NF2 gene in the sporadic counterparts of these NF2-related tumors, we have used reverse transcriptase-PCR amplification followed by SSCP and DNA sequence analysis to screen for mutations in the coding region of the NF2 gene. Analysis of the NF2 gene transcript in 53 unrelated patients with meningiomas and vestibular schwannomas revealed mutations in 32% of the sporadic meningiomas (n = 44), in 50% of the sporadic vestibular schwannomas (n = 4), in 100% of the tumors found in NF2 patients (n = 2), and in one of three tumors from multiple-meningioma patients. Of the 18 tumors in which a mutation in the NF2 gene transcript was observed and the copy number of chromosome 22 could be established, 14 also showed loss of (parts of) chromosome 22. This suggests that in sporadic meningiomas and NF2-associated tumors the NF2 gene functions as a recessive tumor-suppressor gene. The mutations detected resulted mostly in frameshifts, predicting truncations starting within the N-terminal half of the putative protein.
遗传性疾病2型神经纤维瘤病（NF2）的基因与良性中枢神经系统肿瘤（如前庭神经鞘瘤和脑膜瘤）的易感性有关，该基因已被定位到22号染色体上，最近已被分离出来。在散发性脑膜瘤和前庭神经鞘瘤中均发现了NF2基因的突变。然而，到目前为止，该基因的16个外显子中仅分析了6个。为了扩大对NF2基因在这些与NF2相关肿瘤的散发性对应物中作用的分析，我们采用逆转录酶 - PCR扩增，随后进行SSCP和DNA序列分析，以筛选NF2基因编码区的突变。对53例患有脑膜瘤和前庭神经鞘瘤的无关患者的NF2基因转录本进行分析发现，散发性脑膜瘤（n = 44）中有32%发生突变，散发性前庭神经鞘瘤（n = 4）中有50%发生突变，NF2患者的肿瘤（n = 2）中有100%发生突变，以及多发性脑膜瘤患者的三个肿瘤中有一个发生突变。在观察到NF2基因转录本突变且能确定22号染色体拷贝数的18个肿瘤中，有14个还显示出（部分）22号染色体缺失。这表明在散发性脑膜瘤和与NF2相关的肿瘤中，NF2基因作为隐性肿瘤抑制基因发挥作用。检测到的突变大多导致移码，预测在假定蛋白质的N端一半内开始截短。
