GOPC-ROS1 Fusion Due to Microdeletion at 6q22 Is an Oncogenic Driver in a Subset of Pediatric Gliomas and Glioneuronal Tumors

Abstract ROS1 is a transmembrane receptor tyrosine kinase proto-oncogene that has been shown to have rearrangements with several genes in glioblastoma and other neoplasms, including intrachromosomal fusion with GOPC due to microdeletions at 6q22.1. ROS1 fusion events are important findings in these...

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Veröffentlicht in:Journal of neuropathology and experimental neurology 2019-12, Vol.78 (12), p.1089-1099
Hauptverfasser: Richardson, Timothy E, Tang, Karen, Vasudevaraja, Varshini, Serrano, Jonathan, William, Christopher M, Mirchia, Kanish, Pierson, Christopher R, Leonard, Jeffrey R, AbdelBaki, Mohamed S, Schieffer, Kathleen M, Cottrell, Catherine E, Tovar-Spinoza, Zulma, Comito, Melanie A, Boué, Daniel R, Jour, George, Snuderl, Matija
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container_end_page 1099
container_issue 12
container_start_page 1089
container_title Journal of neuropathology and experimental neurology
container_volume 78
creator Richardson, Timothy E
Tang, Karen
Vasudevaraja, Varshini
Serrano, Jonathan
William, Christopher M
Mirchia, Kanish
Pierson, Christopher R
Leonard, Jeffrey R
AbdelBaki, Mohamed S
Schieffer, Kathleen M
Cottrell, Catherine E
Tovar-Spinoza, Zulma
Comito, Melanie A
Boué, Daniel R
Jour, George
Snuderl, Matija
description Abstract ROS1 is a transmembrane receptor tyrosine kinase proto-oncogene that has been shown to have rearrangements with several genes in glioblastoma and other neoplasms, including intrachromosomal fusion with GOPC due to microdeletions at 6q22.1. ROS1 fusion events are important findings in these tumors, as they are potentially targetable alterations with newer tyrosine kinase inhibitors; however, whether these tumors represent a distinct entity remains unknown. In this report, we identify 3 cases of unusual pediatric glioma with GOPC-ROS1 fusion. We reviewed the clinical history, radiologic and histologic features, performed methylation analysis, whole genome copy number profiling, and next generation sequencing analysis for the detection of oncogenic mutation and fusion events to fully characterize the genetic and epigenetic alterations present in these tumors. Two of 3 tumors showed pilocytic features with focal expression of synaptophysin staining and variable high-grade histologic features; the third tumor aligned best with glioblastoma and showed no evidence of neuronal differentiation. Copy number profiling revealed chromosome 6q22 microdeletions corresponding to the GOPC-ROS1 fusion in all 3 cases and methylation profiling showed that the tumors did not cluster together as a single entity or within known methylation classes by t-Distributed Stochastic Neighbor Embedding.
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ROS1 fusion events are important findings in these tumors, as they are potentially targetable alterations with newer tyrosine kinase inhibitors; however, whether these tumors represent a distinct entity remains unknown. In this report, we identify 3 cases of unusual pediatric glioma with GOPC-ROS1 fusion. We reviewed the clinical history, radiologic and histologic features, performed methylation analysis, whole genome copy number profiling, and next generation sequencing analysis for the detection of oncogenic mutation and fusion events to fully characterize the genetic and epigenetic alterations present in these tumors. Two of 3 tumors showed pilocytic features with focal expression of synaptophysin staining and variable high-grade histologic features; the third tumor aligned best with glioblastoma and showed no evidence of neuronal differentiation. Copy number profiling revealed chromosome 6q22 microdeletions corresponding to the GOPC-ROS1 fusion in all 3 cases and methylation profiling showed that the tumors did not cluster together as a single entity or within known methylation classes by t-Distributed Stochastic Neighbor Embedding.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1093/jnen/nlz093</identifier><language>eng</language><publisher>Cary: Oxford University Press</publisher><subject>Brain cancer ; Case studies ; Development and progression ; Gene mutations ; Genetic aspects ; Glioma ; Gliomas ; Health aspects ; Pediatric research ; Pediatrics ; Physiological aspects ; Proto-oncogenes ; Tumors ; Tumors in children</subject><ispartof>Journal of neuropathology and experimental neurology, 2019-12, Vol.78 (12), p.1089-1099</ispartof><rights>2019 American Association of Neuropathologists, Inc. 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subjects Brain cancer
Case studies
Development and progression
Gene mutations
Genetic aspects
Glioma
Gliomas
Health aspects
Pediatric research
Pediatrics
Physiological aspects
Proto-oncogenes
Tumors
Tumors in children
title GOPC-ROS1 Fusion Due to Microdeletion at 6q22 Is an Oncogenic Driver in a Subset of Pediatric Gliomas and Glioneuronal Tumors
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