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 |
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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 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.</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. All rights reserved. 2019</rights><rights>2019 by American Association of Neuropathologists, Inc.</rights><rights>COPYRIGHT 2019 Oxford University Press</rights><rights>2019 American Association of Neuropathologists, Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4743-31fd944f9489bde3d4a448b77cb20158fcba58e5e55b225aad715bf74e8eb6563</citedby><cites>FETCH-LOGICAL-c4743-31fd944f9489bde3d4a448b77cb20158fcba58e5e55b225aad715bf74e8eb6563</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1583,27922,27923</link.rule.ids></links><search><creatorcontrib>Richardson, Timothy E</creatorcontrib><creatorcontrib>Tang, Karen</creatorcontrib><creatorcontrib>Vasudevaraja, Varshini</creatorcontrib><creatorcontrib>Serrano, Jonathan</creatorcontrib><creatorcontrib>William, Christopher M</creatorcontrib><creatorcontrib>Mirchia, Kanish</creatorcontrib><creatorcontrib>Pierson, Christopher R</creatorcontrib><creatorcontrib>Leonard, Jeffrey R</creatorcontrib><creatorcontrib>AbdelBaki, Mohamed S</creatorcontrib><creatorcontrib>Schieffer, Kathleen M</creatorcontrib><creatorcontrib>Cottrell, Catherine E</creatorcontrib><creatorcontrib>Tovar-Spinoza, Zulma</creatorcontrib><creatorcontrib>Comito, Melanie A</creatorcontrib><creatorcontrib>Boué, Daniel R</creatorcontrib><creatorcontrib>Jour, George</creatorcontrib><creatorcontrib>Snuderl, Matija</creatorcontrib><title>GOPC-ROS1 Fusion Due to Microdeletion at 6q22 Is an Oncogenic Driver in a Subset of Pediatric Gliomas and Glioneuronal Tumors</title><title>Journal of neuropathology and experimental neurology</title><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.</description><subject>Brain cancer</subject><subject>Case studies</subject><subject>Development and progression</subject><subject>Gene mutations</subject><subject>Genetic aspects</subject><subject>Glioma</subject><subject>Gliomas</subject><subject>Health aspects</subject><subject>Pediatric research</subject><subject>Pediatrics</subject><subject>Physiological aspects</subject><subject>Proto-oncogenes</subject><subject>Tumors</subject><subject>Tumors in children</subject><issn>0022-3069</issn><issn>1554-6578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kdFr1TAUxoMoeJ0--Q8EBBGkW5ImbfM47tx1MLnDzeeQtqdbrmlylzQbE_zfTa0gyhh5yDknv-8jnA-ht5QcUiLLo50Dd-Tsj1w_QysqBC8qUTfP0YoQxoqSVPIlehXjjhAiieQr9HOzvVgXX7eXFJ-maLzDJwnw5PEX0wXfg4VpHuoJV7eM4bOItcNb1_lrcKbDJ8HcQcAmE_gytREm7Ad8Ab3RU8jvG2v8qGdR_7t2kIJ32uKrNPoQX6MXg7YR3vy5D9C3009X68_F-XZztj4-Lzpe87Io6dBLzgfJG9n2UPZcc960dd21jFDRDF2rRQMChGgZE1r3NRXtUHNooK1EVR6gD4vvPvjbBHFSo4kdWKsd-BQVK0lNy5oxmdF3_6E7n0L-8kxJSSkVhP6lrrUFZdzgp6C72VQdV7ysOJFi9jp8hMqnh9F0eRmDyfN_BB8XQd59jAEGtQ9m1OFBUaLmhNWcsFoSzjRf6HtvJwjxu033ENQNaDvdqBwxEaRmRV6RpCx3xTyaZe8XmU_7J_1_Ac6FtBI</recordid><startdate>20191201</startdate><enddate>20191201</enddate><creator>Richardson, Timothy E</creator><creator>Tang, Karen</creator><creator>Vasudevaraja, Varshini</creator><creator>Serrano, Jonathan</creator><creator>William, Christopher M</creator><creator>Mirchia, Kanish</creator><creator>Pierson, Christopher R</creator><creator>Leonard, Jeffrey R</creator><creator>AbdelBaki, Mohamed S</creator><creator>Schieffer, Kathleen M</creator><creator>Cottrell, Catherine E</creator><creator>Tovar-Spinoza, Zulma</creator><creator>Comito, Melanie A</creator><creator>Boué, Daniel R</creator><creator>Jour, George</creator><creator>Snuderl, Matija</creator><general>Oxford University Press</general><general>by American Association of Neuropathologists, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20191201</creationdate><title>GOPC-ROS1 Fusion Due to Microdeletion at 6q22 Is an Oncogenic Driver in a Subset of Pediatric Gliomas and Glioneuronal Tumors</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4743-31fd944f9489bde3d4a448b77cb20158fcba58e5e55b225aad715bf74e8eb6563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Brain cancer</topic><topic>Case studies</topic><topic>Development and progression</topic><topic>Gene mutations</topic><topic>Genetic aspects</topic><topic>Glioma</topic><topic>Gliomas</topic><topic>Health aspects</topic><topic>Pediatric research</topic><topic>Pediatrics</topic><topic>Physiological aspects</topic><topic>Proto-oncogenes</topic><topic>Tumors</topic><topic>Tumors in children</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Richardson, Timothy E</creatorcontrib><creatorcontrib>Tang, Karen</creatorcontrib><creatorcontrib>Vasudevaraja, Varshini</creatorcontrib><creatorcontrib>Serrano, Jonathan</creatorcontrib><creatorcontrib>William, Christopher M</creatorcontrib><creatorcontrib>Mirchia, Kanish</creatorcontrib><creatorcontrib>Pierson, Christopher R</creatorcontrib><creatorcontrib>Leonard, Jeffrey R</creatorcontrib><creatorcontrib>AbdelBaki, Mohamed S</creatorcontrib><creatorcontrib>Schieffer, Kathleen M</creatorcontrib><creatorcontrib>Cottrell, Catherine E</creatorcontrib><creatorcontrib>Tovar-Spinoza, Zulma</creatorcontrib><creatorcontrib>Comito, Melanie A</creatorcontrib><creatorcontrib>Boué, Daniel R</creatorcontrib><creatorcontrib>Jour, George</creatorcontrib><creatorcontrib>Snuderl, Matija</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of neuropathology and experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Richardson, Timothy E</au><au>Tang, Karen</au><au>Vasudevaraja, Varshini</au><au>Serrano, Jonathan</au><au>William, Christopher M</au><au>Mirchia, Kanish</au><au>Pierson, Christopher R</au><au>Leonard, Jeffrey R</au><au>AbdelBaki, Mohamed S</au><au>Schieffer, Kathleen M</au><au>Cottrell, Catherine E</au><au>Tovar-Spinoza, Zulma</au><au>Comito, Melanie A</au><au>Boué, Daniel R</au><au>Jour, George</au><au>Snuderl, Matija</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GOPC-ROS1 Fusion Due to Microdeletion at 6q22 Is an Oncogenic Driver in a Subset of Pediatric Gliomas and Glioneuronal Tumors</atitle><jtitle>Journal of neuropathology and experimental neurology</jtitle><date>2019-12-01</date><risdate>2019</risdate><volume>78</volume><issue>12</issue><spage>1089</spage><epage>1099</epage><pages>1089-1099</pages><issn>0022-3069</issn><eissn>1554-6578</eissn><abstract>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.</abstract><cop>Cary</cop><pub>Oxford University Press</pub><doi>10.1093/jnen/nlz093</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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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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