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. READ ARTICLE

Cancer Genetics DOI:10.1016/j.cancergen.2020.12.005

Authors: Yiming Zhong, Fumin Lin, Feng Xu, Jeff Schubert, Jinhua Wu, Luanne Wainwright, Xiaonan Zhao, Kajia Cao, Zhiqian Fan, Jiani Chen, Shih-Shan Lang, Benjamin C. Kennedy, Angela N. Viaene, Mariarita Santi, Adam C. Resnick, Phillip B. Storm and Marilyn M. Li