Related Experiment Video
Updated: Apr 16, 2026
Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis
Published on: March 31, 2015
Fusion genes with ALK as recurrent partner in ependymoma-like gliomas: a new brain tumor entity?
Thale Kristin Olsen1, Ioannis Panagopoulos1, Torstein R Meling1
1Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway (T.K.O., I.P., F.M., L.G., J.T., S.H., P.B.); Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway (T.K.O., I.P., F.M., L.G., J.T., S.H., P.B.); Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway (T.K.O., S.H.); Department of Neurosurgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway (T.R.M., B.D.-T.); Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway (M.L.-I., B.K.); Department of Radiology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway (C.S.); Department of Pathology, Rigshospitalet, Copenhagen, Denmark (D.S.); Department of Oncology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway (P.B.).
Background:
We have previously characterized 19 ependymal tumors using Giemsa banding and high-resolution comparative genomic hybridization. The aim of this study was to analyze these tumors searching for fusion genes.
Methods:
RNA sequencing was performed in 12 samples. Potential fusion transcripts were assessed by seed count and structural chromosomal aberrations. Transcripts of interest were validated using fluorescence in situ hybridization and PCR followed by direct sequencing.
Results:
RNA sequencing identified rearrangements of the anaplastic lymphoma kinase gene (ALK) in 2 samples. Both tumors harbored structural aberrations involving the ALK locus 2p23. Tumor 1 had an unbalanced t(2;14)(p23;q22) translocation which led to the fusion gene KTN1-ALK. Tumor 2 had an interstitial del(2)(p16p23) deletion causing the fusion of CCDC88A and ALK. In both samples, the breakpoint of ALK was located between exons 19 and 20. Both patients were infants and both tumors were supratentorial. The tumors were well demarcated from surrounding tissue and had both ependymal and astrocytic features but were diagnosed and treated as ependymomas.
Conclusions:
By combining karyotyping and RNA sequencing, we identified the 2 first ever reported ALK rearrangements in CNS tumors. Such rearrangements may represent the hallmark of a new entity of pediatric glioma characterized by both ependymal and astrocytic features. Our findings are of particular importance because crizotinib, a selective ALK inhibitor, has demonstrated effect in patients with lung cancer harboring ALK rearrangements. Thus, ALK emerges as an interesting therapeutic target in patients with ependymal tumors carrying ALK fusions.
More Related Videos
12:52Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
10:58Transposon Mediated Integration of Plasmid DNA into the Subventricular Zone of Neonatal Mice to Generate Novel Models of Glioblastoma
Published on: February 22, 2015
Related Concept Videos
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20The Retinoblastoma Gene