ALK (Anaplastic lymphoma kinase) fusion proteins are oncogenic and have been seen in various tumors. PPP1CB-ALK fusions are rare but have been reported in a few patients with low- or high-grade gliomas. However, little is known regarding the mechanism of fusion formation and genomic break points of this fusion. We performed genomic characterization of a PPP1CB-ALK fusion with fusion gene amplification in a congenital glioblastoma. The PPP1CB-ALK consists of exons 1–5 of PPP1CB and exons 20–29 of ALK. The genomic translocation breakpoints were determined by real-time quantitative PCR (RT-qPCR) and Sanger sequencing of genomic DNA. Next generation sequencing, RT-qPCR and fluorescence in situ hybridization analyses demonstrated PPP1CB-ALK amplification. Copy number analyses of genes between PPP1CB and ALK using RT-qPCR suggest that the PPP1CB-ALK is likely the result of local chromothripsis followed by episomal amplification. Transcriptome sequencing demonstrated high-level SOX2 expression and predicted WNT/β-catenin pathway activation, suggesting possible therapeutic approaches.

ALK（间变性淋巴瘤激酶）融合蛋白具有致癌性，已在多种肿瘤中发现。PPP1CB - ALK融合蛋白很少见，但在少数低度或高度神经胶质瘤患者中已有报道。然而，关于融合形成的机制和该融合的基因组断裂点知之甚少。我们在先天性胶质母细胞瘤中进行了带有融合基因扩增的PPP1CB-ALK融合的基因组表征。该PPP1CB-ALK由外显子1-5的PPP1CB和外显子20-29 ALK。通过实时定量PCR（RT-qPCR）和基因组DNA的Sanger测序确定基因组易位断点。下一代测序，RT-qPCR和荧​​光原位杂交分析证明了PPP1CB-ALK的扩增。使用RT-qPCR对PPP1CB和ALK之间的基因进行拷贝数分析表明，PPP1CB-ALK可能是局部染色质增生，然后进行游离扩增的结果。转录组测序证明了SOX2的高水平表达并预测了WNT /β-catenin途径的激活，提示了可能的治疗方法。