BCOR has been recognized as a recurrently altered gene in a subset of pediatric tumors of the central nervous system (CNS). Here, we describe a novel BCOR-CREBBP fusion event in a case of pediatric infiltrating astrocytoma and further probe the frequency of related fusion events in CNS tumors. We analyzed biopsy samples taken from a 15-year-old male with an aggressive, unresectable and multifocal infiltrating astrocytoma. We performed RNA sequencing (RNA-seq) and targeted DNA sequencing. In the index case, the fused BCOR-CREBBP transcript comprises exons 1–4 of BCOR and exon 31 of CREBBP. The fused gene thus retains the Bcl6 interaction domain of BCOR while eliminating the domain that has been shown to interact with the polycomb group protein PCGF1. The fusion event was validated by FISH and reverse transcriptase PCR. An additional set of 177 pediatric and adult primary CNS tumors were assessed via FISH for BCOR break apart events, all of which were negative. An additional 509 adult lower grade infiltrating gliomas from the publicly available TCGA dataset were screened for BCOR or CREBBP fusions. In this set, one case was found to harbor a CREBBP-GOLGA6L2 fusion and one case a CREBBP-SRRM2 fusion. In a third patient, both BCOR-L3MBTL2 and EP300-BCOR fusions were seen. Of particular interest to this study, EP300 is a paralog of CREBBP and the breakpoint seen involves a similar region of the gene to that of the index case; however, the resultant transcript is predicted to be completely distinct. While this gene fusion may play an oncogenic role through the loss of tumor suppressor functions of BCOR and CREBBP, further screening over larger cohorts and functional validation is needed to determine the degree to which this or similar fusions are recurrent and to elucidate their oncogenic potential.

中文翻译：

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涉及BCOR和CREBBP的融合蛋白在浸润性神经胶质瘤中很少见。

BCOR已被公认为是中枢神经系统（CNS）儿科肿瘤子集中的反复改变基因。在这里，我们描述了一种在儿科浸润性星形细胞瘤病例中的新型BCOR-CREBBP融合事件，并进一步探讨了中枢神经系统肿瘤中相关融合事件的发生频率。我们分析了从一名15岁男性患有侵袭性，不可切除和多灶性浸润性星形细胞瘤的活检样本。我们进行了RNA测序（RNA-seq）和靶向DNA测序。在索引情况下，融合的BCOR-CREBBP转录本包含BCOR的外显子1-4和CREBBP的外显子31。因此，融合基因保留了BCOR的Bcl6相互作用结构域，同时消除了已显示与多梳基蛋白PCGF1相互作用的结构域。通过FISH和逆转录酶PCR验证了融合事件。通过FISH评估了另一组177例小儿和成人原发性中枢神经系统肿瘤的BCOR分裂事件，所有这些均为阴性。从可公开获得的TCGA数据集中筛选了另外509个成人低度浸润性神经胶质瘤，以进行BCOR或CREBBP融合。在该组中，发现一例带有CREBBP-GOLGA6L2融合物，一例带有CREBBP-SRRM2融合物。在第三位患者中，看到了BCOR-L3MBTL2和EP300-BCOR融合体。这项研究特别令人感兴趣，EP300是CREBBP的旁系同源物，看到的断点涉及与索引病例相似的基因区域。但是，预计生成的成绩单是完全不同的。尽管这种基因融合可能会通过丧失BCOR和CREBBP的抑癌功能发挥致癌作用，