Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55101 Mainz, Germany.
J Neurooncol. 2011 Jul;103(3):437-43. doi: 10.1007/s11060-010-0412-5. Epub 2010 Sep 26.
Vestibular schwannomas (VS) are benign tumors of the nervous system that are usually sporadic but also occur in the inherited disorder neurofibromatosis type 2 (NF2). The NF2 gene is a tumor suppressor gene located on chromosome 22. Loss of the NF2 protein product, Merlin, is universal in both sporadic and NF2-related schwannomas and the loss or mutation of the gene is the only established causative event underlying schwannoma formation. Comparative genomic hybridization (CGH) was used to screen 20 sporadic VS to identify additional chromosomal regions that may harbor genes involved in VS-tumorigenesis. The most common change were losses on chromosome 22q. Additionally, losses were observed on chromosome 9p indicating a possible participation of the CDKN2A tumor suppressor gene in the genesis of VS. Gains were observed on 17q, 19p and 19q, which have been reported before in malignant peripheral nerve sheath tumors that are associated with neurofibromatosis type 1. Importantly, high level amplifications have been observed on 16p and 16q as well as on 9q, suggesting the possible involvement of several oncogenes in the tumorigenesis of VS. Our data suggest the involvement of various oncogenes and tumor suppressor genes might play a role in the genesis of the vestibular schwannomas apart from the inactivation of the NF2 gene.
前庭神经鞘瘤（VS）是神经系统的良性肿瘤，通常为散发性，但也存在于遗传性疾病神经纤维瘤病 2 型（NF2）中。NF2 基因是一种肿瘤抑制基因，位于 22 号染色体上。NF2 蛋白产物 Merlin 的缺失在散发性和 NF2 相关的神经鞘瘤中普遍存在，基因的缺失或突变是神经鞘瘤形成的唯一已确定的致病事件。比较基因组杂交（CGH）用于筛选 20 例散发性 VS，以鉴定可能参与 VS 肿瘤发生的其他染色体区域。最常见的改变是 22q 染色体缺失。此外，还观察到 9p 染色体缺失，表明 CDKN2A 肿瘤抑制基因可能参与 VS 的发生。在与神经纤维瘤病 1 相关的恶性周围神经鞘瘤中，已经报道了 17q、19p 和 19q 的增益。重要的是，还观察到 16p 和 16q 以及 9q 上的高水平扩增，提示几个癌基因可能参与 VS 的肿瘤发生。我们的数据表明，除了 NF2 基因失活外，各种癌基因和肿瘤抑制基因的参与可能在前庭神经鞘瘤的发生中起作用。
