文章：

NF2相关神经鞘瘤病与散发性前庭神经鞘瘤患者的基因变异研究

Genetic Alterations in Patients withNF2-Related Schwannomatosis and Sporadic Vestibular Schwannomas

原文发布日期：24 January 2025

DOI: 10.3390/cancers17030393

类型: Article

开放获取: 是

英文摘要：

Background: Unilateral (uVS) and bilateral vestibular schwannoma (bVS) are distinct disease types, yet share tumorigenic features. This study examined causative genetic alterations in three groups: patients withNF2-related schwannomatosis (NF2), young patients with uVS (≤30 years), and older patients with uVS (≥40 years).Methods: Lymphocyte and vestibular schwannoma DNA was genetically analyzed. Outcomes included gene involvement, pathogenicity classification, variant type, effect, and location, and loss of heterozygosity (LOH) of chromosome 22.Results: Among 93 patients, 17% had NF2, 39% were ≤30 years with uVS, and 44% were ≥40 years with uVS. In all patients with NF2 (100%), two or more hits were detected in the tumor DNA, whereas patients with uVS had a slightly lower detection rate (89–98%). NF2-related tumors had a higher frequency of nucleotide variants (76%), while LOH events were more common in uVS (64–69%). Variants were mostly identified inNF2, with nonsense variants over-represented in patients with NF2 (38%) and frameshift variants more prevalent in uVS (44–51%).Conclusions: BiallelicNF2inactivation primarily drives vestibular schwannoma tumorigenesis. In patients with NF2, two pathogenicNF2variants or oneNF2variant with LOH are common, whereas patients with uVS often exhibit oneNF2variant with LOH. Additionally, variant types differ between patient groups.

摘要翻译： 

背景：单侧前庭神经鞘瘤（uVS）与双侧前庭神经鞘瘤（bVS）属于不同的疾病类型，但具有相似的致瘤特征。本研究针对三组患者探讨其致病性基因改变：神经纤维瘤病2型相关神经鞘瘤病（NF2）患者、年轻单侧前庭神经鞘瘤患者（≤30岁）及年长单侧前庭神经鞘瘤患者（≥40岁）。 方法：对淋巴细胞及前庭神经鞘瘤组织DNA进行遗传学分析。评估指标包括基因参与情况、致病性分类、变异类型、效应与位置，以及22号染色体杂合性缺失（LOH）。 结果：在93例患者中，17%为NF2患者，39%为≤30岁的单侧前庭神经鞘瘤患者，44%为≥40岁的单侧前庭神经鞘瘤患者。所有NF2患者（100%）的肿瘤DNA中均检测到两个及以上基因打击事件，而单侧前庭神经鞘瘤患者的检出率略低（89-98%）。NF2相关肿瘤中核苷酸变异频率较高（76%），而杂合性缺失事件在单侧前庭神经鞘瘤中更为常见（64-69%）。变异主要发生于NF2基因，其中无义变异在NF2患者中占比更高（38%），移码变异则在单侧前庭神经鞘瘤患者中更普遍（44-51%）。 结论：NF2基因双等位基因失活是驱动前庭神经鞘瘤发生的主要机制。NF2患者通常存在两个致病性NF2变异或一个NF2变异伴随杂合性缺失，而单侧前庭神经鞘瘤患者则多表现为一个NF2变异伴随杂合性缺失。此外，不同患者群体间的变异类型存在差异。

原文链接：

Genetic Alterations in Patients withNF2-Related Schwannomatosis and Sporadic Vestibular Schwannomas