Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
Department of Pathology.
J Neuropathol Exp Neurol. 2019 Apr 1;78(4):305-314. doi: 10.1093/jnen/nlz011.
BCOR is an epigenetic regulator and is genetically altered by mutation, deletion, or gene fusion in a range of cancers. "Central nervous system high-grade neuroepithelial tumor with BCOR alteration" is a recently described entity with characteristic internal tandem duplications within exon 15 of the BCOR gene (hereafter: CNS HGNET-BCOR ex15 ITD). In this case series of 3 patients, we report the clinicopathologic, molecular, and methylome features of gliomas with novel EP300-BCOR in-frame gene fusions, thus expanding the spectrum of BCOR alterations seen in CNS tumors. The gliomas in this series arise in children (ages 10-18), involve the supratentorial compartment, and have an infiltrative pattern of growth and a myxoid/microcystic background with frequent psammomatous calcifications and prominent chicken-wire vessels. All 3 cases had areas with low-grade morphology and 2 of them demonstrated histologic high-grade transformation. In contrast to CNS HGNET-BCOR ex15 ITD, they lack perivascular pseudorosettes. On a t-Distributed Stochastic Neighbor Embedding plot they cluster perfectly together, away from CNS HGNET-BCOR ex15ITD, consistent with a different entity. Gliomas with EP300-BCOR fusions and high-grade histology can demonstrate relatively rapid regrowth after debulking or subtotal resection.
BCOR 是一种表观遗传调节剂，在多种癌症中会因突变、缺失或基因融合而改变。“具有 BCOR 改变的中枢神经系统高级神经上皮肿瘤”是一种最近描述的实体，其特征是 BCOR 基因外显子 15 内的串联重复（以下简称：CNS HGNET-BCOR ex15 ITD）。在这 3 例患者的病例系列中，我们报告了具有新型 EP300-BCOR 框内基因融合的神经胶质瘤的临床病理、分子和甲基组学特征，从而扩大了中枢神经系统肿瘤中 BCOR 改变的范围。该系列中的神经胶质瘤发生在儿童（10-18 岁），累及幕上腔，具有浸润性生长模式和黏液样/微囊状背景，常有沙粒状钙化和明显的铁丝网样血管。所有 3 例均有低级别形态区域，其中 2 例表现为组织学高级别转化。与 CNS HGNET-BCOR ex15 ITD 不同，它们缺乏血管周围假玫瑰结。在 t 分布随机邻体嵌入图上，它们完美地聚集在一起，远离 CNS HGNET-BCOR ex15 ITD，这与不同的实体一致。具有 EP300-BCOR 融合和高级别组织学的神经胶质瘤在去瘤或次全切除后可能会迅速复发。
