先天性胶质母细胞瘤中 PPP1CB-ALK 融合体及融合基因扩增的基因组表征.

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. 然而, 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.