Introduction

Vestibular schwannoma (VS) is a benign intracranial tumor in which the underlying genetics is largely uncertain, apart from mutations in the tumor suppressor gene NF2. Alternative tumorigenic mechanisms have been proposed, including a recurrent in-frame fusion transcript of the HTRA1 and SH3PXD2A genes. The gene product of the SH3PXD2A-HTRA1 fusion has been shown to promote proliferation, invasion and resistance to cell death in vitro and tumor growth in vivo. The aim of this study was to replicate the findings and to investigate the frequency of this fusion gene in another cohort of vestibular schwannoma patients.

Methods

The SH3PXD2A-HTRA1 transcript was synthesized in vitro using PCR and used as a positive control to assess the sensitivity of a real-time PCR assay. This real-time PCR assay was used to search for the presence of the fusion transcript in 121 Norwegian sporadic VS patients.

Results

The real-time PCR assay showed a high sensitivity and was able to detect as low as ~ 5 copies of the fusion transcript. Out of the 121 investigated tumors, only 1 harbored the SH3PXD2A-HTRA1 fusion.

Conclusion

Even though the SH3PXD2A-HTRA1 fusion has been shown to be a driver of tumorigenesis, our results suggest that it is a rare event in our VS patients. Further investigation is warranted in order to elucidate whether our results represent an extreme, and if the fusion is present also in other neoplasms.

中文翻译：

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SH3PXD2A-HTRA1 融合转录本在挪威散发性前庭神经鞘瘤患者中极其罕见

 介绍

前庭神经鞘瘤 (VS) 是一种良性颅内肿瘤，除了抑癌基因NF2的突变外，其基本遗传学在很大程度上不确定。已经提出了替代的致瘤机制，包括HTRA1和SH3PXD2A基因的重复框内融合转录本。 SH3PXD2A-HTRA1融合体的基因产物已被证明可促进体外增殖、侵袭和抵抗细胞死亡以及体内肿瘤生长。本研究的目的是复制研究结果并调查另一组前庭神经鞘瘤患者中该融合基因的频率。

 方法

SH3PXD2A-HTRA1转录物是使用 PCR 在体外合成的，并用作阳性对照来评估实时 PCR 测定的灵敏度。该实时 PCR 检测用于在 121 名挪威散发性 VS 患者中寻找融合转录本的存在。

 结果

实时 PCR 检测显示出高灵敏度，能够检测到低至 5 个拷贝的融合转录本。在 121 个研究的肿瘤中，只有 1 个含有SH3PXD2A-HTRA1融合体。

 结论

尽管SH3PXD2A-HTRA1融合已被证明是肿瘤发生的驱动因素，但我们的结果表明，这在我们的 VS 患者中是罕见的事件。有必要进行进一步的研究，以阐明我们的结果是否代表极端情况，以及融合是否也存在于其他肿瘤中。