NF2 Genetic Alterations in Sporadic Vestibular Schwannomas: Clinical Implications
NF2 Genetic Alterations in Sporadic Vestibular Schwannomas: Clinical Implications
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DOI：
10.1097/mao.0b013e318298ac79
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发表时间：
2013-09-01
影响因子：
2.1
通讯作者：
Rey, Juan A.
中科院分区：
文献类型：
--
作者：
Lassaletta, Luis;Torres-Martin, Miguel;Rey, Juan A.
假设：NF 2基因改变可能对非NF 2前庭神经鞘瘤（VS）有临床影响。背景：已有研究表明NF 2基因突变可能与NF 2患者VS的临床表达相关。本研究的目的是分析NF 2基因的遗传改变对散发性VS患者的流行病学、临床和放射学特征的影响。还研究了吸烟与分子遗传学结果之间的关系。研究组包括2006年1月至2010年12月期间在我们机构接受前庭神经鞘瘤手术切除的51例患者。应用5个高度多态性的微卫星DNA标记观察22号染色体的杂合性丢失（洛）频率。采用聚合酶链反应扩增和变性高效液相色谱分析（PCR/dHPLC）检测NF 2基因突变，并对NF 2进行直接测序。结果：49%的病例发现NF 2基因突变，57%的病例发现22 q洛缺失，13.7%的病例发现MLPA改变。在27%的肿瘤中存在一个突变命中，并且在45%的肿瘤中存在2个命中。NF 2突变类型与相关临床参数之间无相关性。通过PCR/dHPLC检测到的NF 2突变的存在与诊断时无听力损失投诉（p = 0.023）、主观耳满（p = 0.022）和没有肿瘤累及内听道（p = 0.029）相关。与无NF 2突变的患者相比，NF 2突变患者的平均校正PTA阈值较低（p = 0.037）。失活的NF 2基因的突变，MLPA，或洛是更频繁的吸烟者相比，从不吸烟者（p = 0.048）。结论：NF 2突变可能发挥作用的病理生理学的听力损失，以及在VS的增长模式。吸烟VS患者似乎发挥作用，在发展肿瘤的风险，也在其遗传特征。需要更多的研究来证实这些结果，更广泛地说，建立分子和临床数据之间的联系。
Hypothesis: NF2 gene alterations may have a clinical impact in non-NF2 vestibular schwannomas (VSs).Background: It has been suggested that NF2 mutations might correlate with clinical expression of VS in NF2 patients. The aim of this study was to analyze the impact of genetic alterations in the NF2 gene on epidemiologic, clinical, and radiologic features of patients with sporadic VS. The association between cigarette consumption and the molecular genetic findings was also studied.Methods: The study group consisted of 51 patients who underwent surgery for removal of vestibular schwannoma in our institution between January 2006 and December 2010. Five 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 using polymerase chain reaction amplification and denaturing high-performance liquid chromatography analysis (PCR/dHPLC), and direct sequencing of NF2. Multiplex ligation-dependent probe amplification (MLPA) of the NF2 gene was also performed.Results: An NF2 mutation was identified in 49%, 22q LOH in 57%, and MLPA alterations in 13.7% of the cases. One mutational hit was present in 27%, and 2 hits were present in 45% of the tumors. No association was found between the type of NF2 mutation and relevant clinical parameters. The presence of NF2 mutations detected by PCR/dHPLC was associated with no complaint of hearing loss at the time of diagnosis (p = 0.023), with subjective aural fullness (p = 0.022) and with an absence of tumor involvement of the internal auditory canal (p = 0.029). Patients with NF2 mutations had lower mean corrected PTA thresholds compared with those with no NF2 mutation (p = 0.037). Inactivation of the NF2 gene by mutation, MLPA, or LOH was more frequent in smokers when compared with never smokers (p = 0.048).Conclusion: NF2 mutations may play a role in the pathophysiology of hearing loss as well as in the pattern of growth of VS. Cigarette smoking in patients with VS seems to play a role in both the risk of developing the tumor and also in its genetic profile. More studies are needed to corroborate these results and, more broadly, to establish links between molecular and clinical data.