unusual loss of EGFR gene copy in glioblastoma multiforme in a child: a case report and analysis of a successfully derived HGG-02 cell line
Purpose The aim of this study was to perform a detailed cytogenetic and molecular genetic analysis of a tumor taken from a 14.5-year-old boy with glioblastoma multiforme who showed an atypical clinical course. Methods Formalin-fixed, paraffin embedded tumor tissue and the corresponding HGG-02 cell l...
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Veröffentlicht in: | Child's nervous system 2010-06, Vol.26 (6), p.841-846 |
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description | Purpose The aim of this study was to perform a detailed cytogenetic and molecular genetic analysis of a tumor taken from a 14.5-year-old boy with glioblastoma multiforme who showed an atypical clinical course. Methods Formalin-fixed, paraffin embedded tumor tissue and the corresponding HGG-02 cell line derived from this tumor were analyzed using fluorescence in situ hybridization (FISH), G-banding, multiplex ligation-dependent probe amplification (MLPA), functional analysis of separated alleles in yeast (FASAY), immunohistochemistry (IHC), and immunocytochemistry (ICC). Results Mutation of the p53 gene and hypermethylation of the MLH1 gene were detected by FASAY and MLPA, respectively. Cytogenetic analysis showed a polyploid karyotype with extensive heterogeneity in chromosome number. Using FISH, we identified a very unusual genetic change - a loss of EGFR gene copy in both the tumor tissue and the HGG-02 cell line. In accordance with the cytogenetic findings, IHC and ICC did not demonstrate overexpression of EGFR in the tumor tissue or HGG-02 cells. Conclusions Despite his very poor prognosis, the patient experienced 34 months of event-free survival after surgery and adjuvant radiotherapy and chemotherapy. The detected loss of the EGFR gene copy may contribute to the unusual biological features of this tumor, but the forthcoming detailed expression analysis of cancer regulatory pathways is necessary to better understand this tumor phenotype. |
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Methods Formalin-fixed, paraffin embedded tumor tissue and the corresponding HGG-02 cell line derived from this tumor were analyzed using fluorescence in situ hybridization (FISH), G-banding, multiplex ligation-dependent probe amplification (MLPA), functional analysis of separated alleles in yeast (FASAY), immunohistochemistry (IHC), and immunocytochemistry (ICC). Results Mutation of the p53 gene and hypermethylation of the MLH1 gene were detected by FASAY and MLPA, respectively. Cytogenetic analysis showed a polyploid karyotype with extensive heterogeneity in chromosome number. Using FISH, we identified a very unusual genetic change - a loss of EGFR gene copy in both the tumor tissue and the HGG-02 cell line. In accordance with the cytogenetic findings, IHC and ICC did not demonstrate overexpression of EGFR in the tumor tissue or HGG-02 cells. Conclusions Despite his very poor prognosis, the patient experienced 34 months of event-free survival after surgery and adjuvant radiotherapy and chemotherapy. The detected loss of the EGFR gene copy may contribute to the unusual biological features of this tumor, but the forthcoming detailed expression analysis of cancer regulatory pathways is necessary to better understand this tumor phenotype.</description><identifier>ISSN: 0256-7040</identifier><identifier>EISSN: 1433-0350</identifier><identifier>DOI: 10.1007/s00381-010-1110-5</identifier><identifier>PMID: 20195615</identifier><language>eng</language><publisher>Berlin/Heidelberg: Berlin/Heidelberg : Springer-Verlag</publisher><subject>Adaptor Proteins, Signal Transducing - genetics ; Adolescent ; Brain - metabolism ; Brain - pathology ; Brain Neoplasms - genetics ; Brain Neoplasms - pathology ; Brain Neoplasms - therapy ; Case Report ; Cell Line, Tumor ; Disease Progression ; EGFR ; FASAY ; fish ; Gene Dosage ; Genes, p53 ; Glioblastoma - genetics ; Glioblastoma - pathology ; Glioblastoma - therapy ; Glioblastoma multiforme ; Humans ; karyotyping ; Male ; Medicine ; Medicine & Public Health ; Mutation ; MutL Protein Homolog 1 ; Neurosciences ; Neurosurgery ; Nuclear Proteins - genetics ; p53 ; Phenotype ; Receptor, Epidermal Growth Factor - genetics ; Treatment Outcome</subject><ispartof>Child's nervous system, 2010-06, Vol.26 (6), p.841-846</ispartof><rights>Springer-Verlag 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-c6f9bf65da124be628b4011250558ebc26016563d81ebb24f53f74eb5a73ba0f3</citedby><cites>FETCH-LOGICAL-c399t-c6f9bf65da124be628b4011250558ebc26016563d81ebb24f53f74eb5a73ba0f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00381-010-1110-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00381-010-1110-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20195615$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Veselska, Renata</creatorcontrib><creatorcontrib>Skoda, Jan</creatorcontrib><creatorcontrib>Loja, Tomas</creatorcontrib><creatorcontrib>Zitterbart, Karel</creatorcontrib><creatorcontrib>Pavelka, Zdenek</creatorcontrib><creatorcontrib>Smardova, Jana</creatorcontrib><creatorcontrib>Valaskova, Iveta</creatorcontrib><creatorcontrib>Hermanova, Marketa</creatorcontrib><creatorcontrib>Sterba, Jaroslav</creatorcontrib><title>unusual loss of EGFR gene copy in glioblastoma multiforme in a child: a case report and analysis of a successfully derived HGG-02 cell line</title><title>Child's nervous system</title><addtitle>Childs Nerv Syst</addtitle><addtitle>Childs Nerv Syst</addtitle><description>Purpose The aim of this study was to perform a detailed cytogenetic and molecular genetic analysis of a tumor taken from a 14.5-year-old boy with glioblastoma multiforme who showed an atypical clinical course. Methods Formalin-fixed, paraffin embedded tumor tissue and the corresponding HGG-02 cell line derived from this tumor were analyzed using fluorescence in situ hybridization (FISH), G-banding, multiplex ligation-dependent probe amplification (MLPA), functional analysis of separated alleles in yeast (FASAY), immunohistochemistry (IHC), and immunocytochemistry (ICC). Results Mutation of the p53 gene and hypermethylation of the MLH1 gene were detected by FASAY and MLPA, respectively. Cytogenetic analysis showed a polyploid karyotype with extensive heterogeneity in chromosome number. Using FISH, we identified a very unusual genetic change - a loss of EGFR gene copy in both the tumor tissue and the HGG-02 cell line. In accordance with the cytogenetic findings, IHC and ICC did not demonstrate overexpression of EGFR in the tumor tissue or HGG-02 cells. Conclusions Despite his very poor prognosis, the patient experienced 34 months of event-free survival after surgery and adjuvant radiotherapy and chemotherapy. The detected loss of the EGFR gene copy may contribute to the unusual biological features of this tumor, but the forthcoming detailed expression analysis of cancer regulatory pathways is necessary to better understand this tumor phenotype.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adolescent</subject><subject>Brain - metabolism</subject><subject>Brain - pathology</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain Neoplasms - therapy</subject><subject>Case Report</subject><subject>Cell Line, Tumor</subject><subject>Disease Progression</subject><subject>EGFR</subject><subject>FASAY</subject><subject>fish</subject><subject>Gene Dosage</subject><subject>Genes, p53</subject><subject>Glioblastoma - genetics</subject><subject>Glioblastoma - pathology</subject><subject>Glioblastoma - therapy</subject><subject>Glioblastoma multiforme</subject><subject>Humans</subject><subject>karyotyping</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mutation</subject><subject>MutL Protein Homolog 1</subject><subject>Neurosciences</subject><subject>Neurosurgery</subject><subject>Nuclear Proteins - genetics</subject><subject>p53</subject><subject>Phenotype</subject><subject>Receptor, Epidermal Growth Factor - genetics</subject><subject>Treatment Outcome</subject><issn>0256-7040</issn><issn>1433-0350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1v1DAUjBCIbgs_gAv4xinwbMeJww1V7RapEhLQs2Unz4srJ17sGGl_A38apykc4eCPpzczfp6pqlcU3lGA7n0C4JLWQKGmtGziSbWjDec1cAFPqx0w0dYdNHBWnad0D0CFZP3z6owB7UVLxa76leecsvbEh5RIsORqf_2FHHBGMoTjibiZHLwLxuu0hEmTKfvF2RAnXFuaDN-dHz-sF52QRDyGuBA9j2Vpf0ruQVOTlIcBU7LZ-xMZMbqfOJKb_b4GRgb05Xk344vqmdU-4cvH86K6u776dnlT337ef7r8eFsPvO-Xemhtb2wrRk1ZY7Bl0jRAKRMghEQzsBZoK1o-SorGsMYKbrsGjdAdNxosv6jebrrHGH5kTIuaXFqn0DOGnFQnGtmD7OX_kbwY3ctmRdINOcRiZESrjtFNOp4UBbWGpbawFKx1CUuJwnn9qJ7NhONfxp90CoBtgFRa8wGjug85FmPTP1XfbCSrg9KH6JK6-1okOVDZ0PI3_hu0oqff</recordid><startdate>20100601</startdate><enddate>20100601</enddate><creator>Veselska, Renata</creator><creator>Skoda, Jan</creator><creator>Loja, Tomas</creator><creator>Zitterbart, Karel</creator><creator>Pavelka, Zdenek</creator><creator>Smardova, Jana</creator><creator>Valaskova, Iveta</creator><creator>Hermanova, Marketa</creator><creator>Sterba, Jaroslav</creator><general>Berlin/Heidelberg : Springer-Verlag</general><general>Springer-Verlag</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7TK</scope></search><sort><creationdate>20100601</creationdate><title>unusual loss of EGFR gene copy in glioblastoma multiforme in a child: a case report and analysis of a successfully derived HGG-02 cell line</title><author>Veselska, Renata ; Skoda, Jan ; Loja, Tomas ; Zitterbart, Karel ; Pavelka, Zdenek ; Smardova, Jana ; Valaskova, Iveta ; Hermanova, Marketa ; Sterba, Jaroslav</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c399t-c6f9bf65da124be628b4011250558ebc26016563d81ebb24f53f74eb5a73ba0f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adolescent</topic><topic>Brain - metabolism</topic><topic>Brain - pathology</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - pathology</topic><topic>Brain Neoplasms - therapy</topic><topic>Case Report</topic><topic>Cell Line, Tumor</topic><topic>Disease Progression</topic><topic>EGFR</topic><topic>FASAY</topic><topic>fish</topic><topic>Gene Dosage</topic><topic>Genes, p53</topic><topic>Glioblastoma - genetics</topic><topic>Glioblastoma - pathology</topic><topic>Glioblastoma - therapy</topic><topic>Glioblastoma multiforme</topic><topic>Humans</topic><topic>karyotyping</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mutation</topic><topic>MutL Protein Homolog 1</topic><topic>Neurosciences</topic><topic>Neurosurgery</topic><topic>Nuclear Proteins - genetics</topic><topic>p53</topic><topic>Phenotype</topic><topic>Receptor, Epidermal Growth Factor - genetics</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Veselska, Renata</creatorcontrib><creatorcontrib>Skoda, Jan</creatorcontrib><creatorcontrib>Loja, Tomas</creatorcontrib><creatorcontrib>Zitterbart, Karel</creatorcontrib><creatorcontrib>Pavelka, Zdenek</creatorcontrib><creatorcontrib>Smardova, Jana</creatorcontrib><creatorcontrib>Valaskova, Iveta</creatorcontrib><creatorcontrib>Hermanova, Marketa</creatorcontrib><creatorcontrib>Sterba, Jaroslav</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Neurosciences Abstracts</collection><jtitle>Child's nervous system</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Veselska, Renata</au><au>Skoda, Jan</au><au>Loja, Tomas</au><au>Zitterbart, Karel</au><au>Pavelka, Zdenek</au><au>Smardova, Jana</au><au>Valaskova, Iveta</au><au>Hermanova, Marketa</au><au>Sterba, Jaroslav</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>unusual loss of EGFR gene copy in glioblastoma multiforme in a child: a case report and analysis of a successfully derived HGG-02 cell line</atitle><jtitle>Child's nervous system</jtitle><stitle>Childs Nerv Syst</stitle><addtitle>Childs Nerv Syst</addtitle><date>2010-06-01</date><risdate>2010</risdate><volume>26</volume><issue>6</issue><spage>841</spage><epage>846</epage><pages>841-846</pages><issn>0256-7040</issn><eissn>1433-0350</eissn><abstract>Purpose The aim of this study was to perform a detailed cytogenetic and molecular genetic analysis of a tumor taken from a 14.5-year-old boy with glioblastoma multiforme who showed an atypical clinical course. Methods Formalin-fixed, paraffin embedded tumor tissue and the corresponding HGG-02 cell line derived from this tumor were analyzed using fluorescence in situ hybridization (FISH), G-banding, multiplex ligation-dependent probe amplification (MLPA), functional analysis of separated alleles in yeast (FASAY), immunohistochemistry (IHC), and immunocytochemistry (ICC). Results Mutation of the p53 gene and hypermethylation of the MLH1 gene were detected by FASAY and MLPA, respectively. Cytogenetic analysis showed a polyploid karyotype with extensive heterogeneity in chromosome number. Using FISH, we identified a very unusual genetic change - a loss of EGFR gene copy in both the tumor tissue and the HGG-02 cell line. In accordance with the cytogenetic findings, IHC and ICC did not demonstrate overexpression of EGFR in the tumor tissue or HGG-02 cells. Conclusions Despite his very poor prognosis, the patient experienced 34 months of event-free survival after surgery and adjuvant radiotherapy and chemotherapy. The detected loss of the EGFR gene copy may contribute to the unusual biological features of this tumor, but the forthcoming detailed expression analysis of cancer regulatory pathways is necessary to better understand this tumor phenotype.</abstract><cop>Berlin/Heidelberg</cop><pub>Berlin/Heidelberg : Springer-Verlag</pub><pmid>20195615</pmid><doi>10.1007/s00381-010-1110-5</doi><tpages>6</tpages></addata></record> |
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subjects | Adaptor Proteins, Signal Transducing - genetics Adolescent Brain - metabolism Brain - pathology Brain Neoplasms - genetics Brain Neoplasms - pathology Brain Neoplasms - therapy Case Report Cell Line, Tumor Disease Progression EGFR FASAY fish Gene Dosage Genes, p53 Glioblastoma - genetics Glioblastoma - pathology Glioblastoma - therapy Glioblastoma multiforme Humans karyotyping Male Medicine Medicine & Public Health Mutation MutL Protein Homolog 1 Neurosciences Neurosurgery Nuclear Proteins - genetics p53 Phenotype Receptor, Epidermal Growth Factor - genetics Treatment Outcome |
title | unusual loss of EGFR gene copy in glioblastoma multiforme in a child: a case report and analysis of a successfully derived HGG-02 cell line |
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