Astrocytomas that harbor recurrent genomic alterations in MYB or MYBL1 are a group of Pediatric-type diffuse low-grade gliomas that were newly recognized in the 2021 WHO Classification of Tumors of the Central Nervous System. These tumors are described in the WHO classification as harboring fusions in MYB or MYBL1. In this report, we examine 14 consecutive cases in which a MYB or MYBL1 alteration was identified, each with diagnostic confirmation by genome-wide DNA methylation profiling (6 Angiocentric gliomas and 8 Diffuse astrocytomas, MYB- or MYBL1-altered), for their specific genomic alterations in these genes. Using RNA sequencing, we find productive in-frame fusions of the MYB or MYBL1 genes in only 5/14 cases. The remaining 9 cases show genomic alterations that result in truncation of the gene, without evidence of an in-frame fusion partner. Gene expression analysis showed overexpression of the MYB(L1) genes, regardless of the presence of a productive fusion. In addition, QKI, a recognized fusion partner common in angiocentric glioma, was generally up-regulated in these 14 cases, compared to a cohort comprising >1000 CNS tumors of various types, regardless of whether a genomic alteration in QKI was present. Overall, the results show that truncations, in the absence of a productive fusion, of the MYB(L1) genes can likely drive the tumors and have implications for the analysis and diagnosis of Angiocentric glioma and Diffuse astrocytoma, MYB- or MYBL1-altered, especially for cases that are tested on panels designed to focus on fusion detection.

携带 MYB 或 MYBL1 复发性基因组改变的星形细胞瘤是一组儿科型弥漫性低级别胶质瘤，在 2021 年 WHO 中枢神经系统肿瘤分类中新发现。这些肿瘤在 WHO 分类中被描述为 MYB 或 MYBL1 融合。在本报告中，我们检查了 14 个连续发现 MYB 或 MYBL1 改变的病例，每个病例都通过全基因组 DNA 甲基化分析（6 个血管中心神经胶质瘤和 8 个弥漫性星形细胞瘤，MYB 或 MYBL1 改变）进行诊断确认，因为它们在这些基因中的特定基因组改变。使用 RNA 测序，我们仅在 5/14 的情况下发现 MYB 或 MYBL1 基因的高效框内融合。其余 9 例显示导致基因截断的基因组改变，没有框内融合伴侣的证据。基因表达分析显示 MYB （L1） 基因过表达，无论是否存在生产性融合。此外，与包含各种类型的 >1000 个 CNS 肿瘤的队列相比，QKI 是血管中心性胶质瘤中公认的融合伴侣，在这 14 例中通常上调，无论是否存在 QKI 的基因组改变。总体而言，结果表明，在没有有效融合的情况下，MYB （L1） 基因的截断可能会驱动肿瘤，并对血管中心性胶质瘤和弥漫性星形细胞瘤、MYB 或 MYBL1 改变的分析和诊断产生影响，特别是对于在旨在专注于融合检测的面板上进行测试的病例。