Genomic characterization of a PPP1CB-ALK fusion with fusion gene amplification in a congenital glioblastoma

Cancer Genet. 2021 Apr:252-253:37-42. doi: 10.1016/j.cancergen.2020.12.005. Epub 2020 Dec 11.

Abstract

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.

Keywords: Gene amplification; Glioblastoma; NGS; PPP1CB-ALK fusion.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaplastic Lymphoma Kinase / genetics*
  • Brain Neoplasms / congenital*
  • Brain Neoplasms / genetics
  • Exons
  • Female
  • Gene Amplification*
  • Glioblastoma / congenital*
  • Glioblastoma / genetics
  • Humans
  • Infant, Newborn
  • Protein Phosphatase 1 / genetics*
  • RNA, Messenger / genetics
  • Recombinant Fusion Proteins / genetics

Substances

  • RNA, Messenger
  • Recombinant Fusion Proteins
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • PPP1CB protein, human
  • Protein Phosphatase 1