PDF(Pubmed)
Abstract：
Gene fusion events have been linked to oncogenesis in many cancers. However, gene fusions in meningioma are understudied compared to somatic mutations, chromosomal gains/losses, and epigenetic changes. Fusions involving B-raf proto-oncogene, serine/threonine kinase (BRAF) are subtypes of oncogenic BRAF genetic abnormalities that have been reported in certain cases of brain tumors, such as pilocytic astrocytomas. However, BRAF fusions have not been recognized in meningioma. We present the case of an adult female presenting with episodic partial seizures characterized by déjà vu, confusion, and cognitive changes. Brain imaging revealed a cavernous sinus and sphenoid wing mass and she underwent resection. Histopathology revealed a World Health Organization (WHO) grade 1 meningioma. Genetic profiling with next generation sequencing and microarray analysis revealed an in-frame BRAF::PTPRN2 fusion affecting the BRAF kinase domain as well as chromothripsis of chromosome 7q resulting in multiple segmental gains and losses including amplifications of cyclin dependent kinase 6 (CDK6), tyrosine protein-kinase Met (MET), and smoothened (SMO). Elevated pERK staining in tumor cells provided evidence of activated mitogen-activated protein kinase (MAPK) signaling. This report raises the possibility that gene fusion events may be involved in meningioma pathogenesis and warrant further investigation.
摘要：
基因融合事件与许多癌症的发生有关。然而,与体细胞突变相比，脑膜瘤的基因融合研究不足，染色体增益/损失，和表观遗传变化。涉及B-raf原癌基因的融合，丝氨酸/苏氨酸激酶（BRAF）是致癌BRAF遗传异常的亚型，在某些脑肿瘤病例中已报道。如毛细胞星形细胞瘤。然而,在脑膜瘤中尚未发现BRAF融合。我们介绍了一名成年女性的病例，其特征是似曾相识的发作性部分癫痫发作，混乱,和认知变化。脑成像显示海绵窦和蝶骨翼肿块，她接受了切除术。组织病理学显示世界卫生组织（WHO）1级脑膜瘤。下一代测序和微阵列分析的遗传谱分析显示，框架内的BRAF::PTPRN2融合影响BRAF激酶结构域以及染色体7q的染色体，导致多个片段的得失，包括细胞周期蛋白依赖性激酶6（CDK6）的扩增，酪氨酸蛋白激酶Met（MET），和平滑（SMO）。肿瘤细胞中pERK染色的升高提供了激活的丝裂原激活的蛋白激酶（MAPK）信号传导的证据。该报告提出了基因融合事件可能参与脑膜瘤发病机制的可能性，需要进一步研究。
