Genomic Characterization of a PPP1CB-ALK Fusion with Fusion Gene Amplification in a Congenital Glioblastoma
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.
- A PPP1CB-ALK fusion with fusion gene amplification was identified in the congenital glioblastoma.
- The genomic translocation breakpoints were mapped to chr2:29006845-29006910 for PPP1CB and chr2:29446692-29447359 for ALK.
- Some of the genes between PPP1CB and ALK were amplified along with the PPP1CB-ALK.
- The PPP1CB-ALK fusion was most likely caused by a local chromothripsis event followed by episomal amplification.
- Transcriptome sequencing demonstrated high-level SOX2 expression and predicted WNT/β-catenin pathway activation.