散发性前庭神经鞘瘤NF2基因的综合遗传分析

IF 1.7 4区医学 Q2 OTORHINOLARYNGOLOGY

Laryngoscope Investigative Otolaryngology Pub Date : 2025-09-27 DOI:10.1002/lio2.70265

Takeshi Wakabayashi, Koichiro Wasano, Kohei Nakamura, Makoto Hosoya, Ryutaro Kawano, Reika Takamatsu, Masafumi Ueno, Marie N. Shimanuki, Nobuyoshi Tsuzuki, Takanori Nishiyama, Takenori Akiyama, Masahiro Toda, Hiroshi Nishihara, Hiroyuki Ozawa, Naoki Oishi

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引用次数: 0

摘要

目的探讨散发性前庭神经鞘瘤（VSs）的遗传病因，探讨NF2失活机制与术前临床特征（包括听力功能和肿瘤生长）的相关性。方法选取2020年6月至2022年3月在我院耳鼻喉科或神经外科行VS切除术的19例患者为研究对象。采用全外显子组测序（WES）检测NF2的体细胞变化。此外，使用甲基化分析和多重连接依赖探针扩增（MLPA）评估NF2启动子甲基化状态和拷贝数变化。收集术前临床数据，包括纯音听力学、言语辨别评分和肿瘤生长速率，并分析其与遗传结果的相关性。结果WES检测到16例（84.2%）患者NF2等位基因均存在体细胞改变。甲基化分析和MLPA证实了所有病例中双等位基因NF2失活。NF2启动子甲基化被认为与听力损失和肿瘤进展有关。NF2表达水平与肿瘤生长速率呈弱相关（r = 0.21），而NF2表达水平与纯音听力或言语辨别评分无显著相关性。结论综合遗传分析，包括WES、甲基化分析和MLPA分析，是确定散发性VSs中NF2失活机制的必要手段。研究结果表明NF2甲基化可能导致临床表现的变化。需要更大规模的进一步研究来阐明表观遗传修饰在疾病进展中的作用及其对患者管理策略的潜在影响。证据级别4。

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Comprehensive Genetic Analysis of NF2 in Sporadic Vestibular Schwannoma

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Comprehensive Genetic Analysis of NF2 in Sporadic Vestibular Schwannoma

Objective

To elucidate the genetic etiology of sporadic vestibular schwannomas (VSs) and investigate the correlation between NF2 inactivation mechanisms and preoperative clinical characteristics, including hearing function and tumor growth.

Methods

Nineteen patients who underwent VS resection at our otorhinolaryngology or neurosurgery department between June 2020 and March 2022 were included in this study. Whole-exome sequencing (WES) was performed to detect somatic changes in NF2. Additionally, NF2 promoter methylation status and copy number changes were evaluated using methylation analysis and multiple ligation-dependent probe amplification (MLPA). Preoperative clinical data, including pure tone audiometry, speech discrimination scores, and tumor growth rates, were collected and analyzed for correlations with genetic findings.

Results

WES identified somatic alterations in both NF2 alleles in 16 cases (84.2%). The addition of methylation analysis and MLPA confirmed biallelic NF2 inactivation in all cases. NF2 promoter methylation was suggested to be associated with hearing loss and tumor progression. A weak correlation between NF2 expression levels and tumor growth rate was observed (r = 0.21), while no significant correlation was found between NF2 expression and pure tone audiometry or speech discrimination scores.

Conclusion

Comprehensive genetic analyses, including WES, methylation analysis, and MLPA, are essential for identifying NF2 inactivation mechanisms in sporadic VSs. The findings suggest that NF2 methylation may contribute to variations in clinical presentation. Further studies with larger cohorts are necessary to clarify the role of epigenetic modifications in disease progression and their potential impact on patient management strategies.