Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada.
Department of Pathobiology and Laboratory Medicine, University of Toronto, Toronto, ON, Canada.
Mod Pathol. 2021 Jun;34(6):1116-1124. doi: 10.1038/s41379-021-00783-0. Epub 2021 Mar 1.
Benign peripheral nerve tumors include schwannoma, neurofibroma, and perineurioma, as well as a recently recognized group of tumors with dual patterns of differentiation. The molecular pathogenesis of these so-called "hybrid" tumors remains poorly understood. Following identification of a novel CHD7-VGLL3 fusion gene in a hybrid schwannoma-perineurioma, we evaluated an expanded cohort of this tumor-type-as well as tumors with VGLL3 rearrangement identified from a curated molecular database-to characterize the prevalence of fusion genes among these tumors. Eighteen tumors met the inclusion criteria for this study. RNA sequencing identified VGLL3 rearrangement in 14 of these cases; the partner genes included CHD7 (ten cases), CHD9 (two cases), and MAMLD1 (two cases). Two cases possessed altogether unrelated fusions, including: DST-BRAF and SQSTM1-CDX1 fusion genes. Finally, two cases lacked identifiable fusion products. These findings highlight the molecular diversity of these neoplasms, with frequent rearrangement of VGLL3. More importantly, despite their dual pattern of differentiation, our results reveal the pathogenesis of hybrid schwannoma-perineurioma is unrelated to conventional schwannoma and perineurioma, thereby implying this tumor represents an altogether pathologically distinct entity.
良性周围神经肿瘤包括神经鞘瘤、神经纤维瘤和周围神经细胞瘤，以及最近发现的一组具有双重分化模式的肿瘤。这些所谓的“混合”肿瘤的分子发病机制仍知之甚少。在混合性神经鞘瘤-周围神经细胞瘤中鉴定出一种新型 CHD7-VGLL3 融合基因后，我们评估了该肿瘤类型的一个扩展队列，以及从经过精心整理的分子数据库中鉴定出的具有 VGLL3 重排的肿瘤，以确定这些肿瘤中融合基因的普遍性。有 18 个肿瘤符合本研究的纳入标准。RNA 测序在其中 14 例中鉴定出 VGLL3 重排；这些基因的伙伴包括 CHD7（10 例）、CHD9（2 例）和 MAMLD1（2 例）。2 例具有完全无关的融合，包括 DST-BRAF 和 SQSTM1-CDX1 融合基因。最后，2 例缺乏可识别的融合产物。这些发现突出了这些肿瘤的分子多样性，VGLL3 频繁重排。更重要的是，尽管它们具有双重分化模式，但我们的结果表明，混合性神经鞘瘤-周围神经细胞瘤的发病机制与传统的神经鞘瘤和周围神经细胞瘤无关，因此暗示该肿瘤代表一种完全不同的病理实体。
