Abstract
The proto-oncogene tyrosine-protein kinase ROS1 (ROS1) is a tyrosine kinase that is closely related to anaplastic lymphoma kinase receptor (ALK). We describe a novel KLC1-ROS1 fusion identified in a case of pediatric low-grade glioma. This was detected by RNA sequencing and confirmed by reverse-transcription PCR and fluorescent in situ hybridization. Immunohistochemical staining for ROS1 was positive in the tumor cytoplasm. In vitro analysis demonstrated the oncogenic activity of this fusion, which was suppressed by the ALK/ROS1 inhibitor, crizotinib. Our case and others suggest that various ROS1 fusions might be present in a subset of pediatric gliomas, which could be targeted for therapy.
Keywords:
Crizotinib; FISH; Immunohistochemistry; KLC1–ROS1 fusion; Pediatric glioma.
MeSH terms
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Brain Neoplasms / drug therapy
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Brain Neoplasms / genetics*
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Brain Neoplasms / pathology*
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Child, Preschool
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Crizotinib / pharmacology
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Female
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Gene Fusion* / drug effects
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Glioma / drug therapy
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Glioma / genetics*
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Glioma / pathology*
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Humans
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Immunohistochemistry
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In Situ Hybridization, Fluorescence
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Kinesins
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Microtubule-Associated Proteins / genetics*
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Molecular Targeted Therapy
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Neoplasm Staging
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Protein-Tyrosine Kinases / genetics*
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Protein-Tyrosine Kinases / metabolism
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Proto-Oncogene Mas
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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KLC1 protein, human
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MAS1 protein, human
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Microtubule-Associated Proteins
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Proto-Oncogene Mas
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Proto-Oncogene Proteins
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Crizotinib
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Protein-Tyrosine Kinases
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ROS1 protein, human
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Kinesins