Pediatric Neuro-Oncology Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Department of Neurosurgery, Weill Cornell Medicine and Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Acta Neuropathol Commun. 2022 Aug 19;10(1):117. doi: 10.1186/s40478-022-01423-7.
Biallelic inactivation of NF2 represents the primary or sole oncogenic driver event in the vast majority of schwannomas. We report on a four-year-old female who underwent subtotal resection of a right medullary intraparenchymal schwannoma. RNA sequencing revealed an in-frame fusion between exon 5 of YAP1 and exon 2 of MAML2. YAP1-MAML2 fusions have previously been reported in a variety of tumor types, but not schwannomas. Our report expands the spectrum of oncogenic YAP1 gene fusions an alternative to NF2 inactivation to include sporadic schwannoma, analogous to what has recently been described in NF2-wildtype pediatric meningiomas. Appropriate somatic and germline molecular testing should be undertaken in all young patients with solitary schwannoma and meningioma given the high prevalence of an underlying tumor predisposition syndrome. In such patients, the identification of a somatic non-NF2 driver alteration such as this newly described YAP1 fusion, can help ascertain the diagnosis of a sporadic schwannoma.
NF2 的双等位基因失活是绝大多数神经鞘瘤中主要或唯一的致癌驱动事件。我们报告了一例 4 岁女性，她接受了右延髓脑实质内神经鞘瘤的次全切除术。RNA 测序显示 YAP1 外显子 5 与 MAML2 外显子 2 之间存在框内融合。YAP1-MAML2 融合已在多种肿瘤类型中报道，但不在神经鞘瘤中。我们的报告扩展了致癌 YAP1 基因融合的范围，为包括散发性神经鞘瘤在内的 NF2 失活提供了另一种选择，类似于最近在 NF2 野生型小儿脑膜瘤中描述的情况。鉴于潜在的肿瘤易感性综合征的高患病率，对于所有患有单发神经鞘瘤和脑膜瘤的年轻患者，应进行适当的体细胞和种系分子检测。在这些患者中，鉴定出一种体细胞非 NF2 驱动改变，如这种新描述的 YAP1 融合，有助于确定散发性神经鞘瘤的诊断。
