Novel Molecular Stereotactic Biopsy Procedures Reveal Intratumoral Homogeneity of Loss of Heterozygosity of 1p/19q and TP53 Mutations in World Health Organization Grade II Gliomas
We report a molecular stereotactic biopsy technique that combines histopathologic diagnosis with small sample size-adjusted molecular genetic analysis of low-grade gliomas that are ineligible for tumor resection. Loss of heterozygosity (LOH) of 1p/19q and TP53 mutationswere analyzed in 1-mm tissue s...
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| Veröffentlicht in: | Journal of neuropathology and experimental neurology 2009-11, Vol.68 (11), p.1219-1228 |
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| container_title | Journal of neuropathology and experimental neurology |
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| creator | Thon, Niklas Eigenbrod, Sabina Grasbon-Frodl, Eva M Ruiter, Michael Mehrkens, Jan H Kreth, Simone Tonn, Jörg C Kretzschmar, Hans A Kreth, Friedrich W |
| description | We report a molecular stereotactic biopsy technique that combines histopathologic diagnosis with small sample size-adjusted molecular genetic analysis of low-grade gliomas that are ineligible for tumor resection. Loss of heterozygosity (LOH) of 1p/19q and TP53 mutationswere analyzed in 1-mm tissue samples from 42 World Health Organization grade II gliomas (30 astrocytomas, 8 oligoastrocytomas, 4 oligodendrogliomas) using polymerase chain reaction-based microsatellite and sequence analysis. Alternating histological and molecular genetic evaluation within 1-mm steps at different sites within each tumor was performed to determine reproducibility of the results and the intratumoral distribution of the biomarkers. Multiple serial biopsies (range, 2-5 per tumor) taken from distinct intratumoral areas revealed concordant molecular genetic findings and homogeneous distribution of both biomarkers throughout 41 tumors. Contamination by nonneoplastic tissue could be recognized by corresponding histological evaluation and resulted in discordant LOH findings in 1 tumor. The frequency of LOH 1p/19q and TP53 mutations was consistent with the literature; these genetic alterations were found to be mutually exclusive. There was no biopsy-related morbidity. We conclude that determination of the LOH 1p/19q and TP53 status using this molecular stereotactic biopsy technique is safe and reliable in cases of unresectable gliomas. |
| doi_str_mv | 10.1097/NEN.0b013e3181bee1f1 |
| format | Article |
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Loss of heterozygosity (LOH) of 1p/19q and TP53 mutationswere analyzed in 1-mm tissue samples from 42 World Health Organization grade II gliomas (30 astrocytomas, 8 oligoastrocytomas, 4 oligodendrogliomas) using polymerase chain reaction-based microsatellite and sequence analysis. Alternating histological and molecular genetic evaluation within 1-mm steps at different sites within each tumor was performed to determine reproducibility of the results and the intratumoral distribution of the biomarkers. Multiple serial biopsies (range, 2-5 per tumor) taken from distinct intratumoral areas revealed concordant molecular genetic findings and homogeneous distribution of both biomarkers throughout 41 tumors. Contamination by nonneoplastic tissue could be recognized by corresponding histological evaluation and resulted in discordant LOH findings in 1 tumor. The frequency of LOH 1p/19q and TP53 mutations was consistent with the literature; these genetic alterations were found to be mutually exclusive. There was no biopsy-related morbidity. We conclude that determination of the LOH 1p/19q and TP53 status using this molecular stereotactic biopsy technique is safe and reliable in cases of unresectable gliomas.</description><identifier>ISSN: 0022-3069</identifier><identifier>EISSN: 1554-6578</identifier><identifier>DOI: 10.1097/NEN.0b013e3181bee1f1</identifier><identifier>PMID: 19816195</identifier><identifier>CODEN: JNENAD</identifier><language>eng</language><publisher>England: American Association of Neuropathologists, Inc</publisher><subject>Adolescent ; Adult ; Aged ; Astrocytoma - genetics ; Astrocytoma - pathology ; Chromosomes, Human, Pair 1 - genetics ; Chromosomes, Human, Pair 19 - genetics ; Female ; Glioma - genetics ; Glioma - pathology ; Humans ; Loss of Heterozygosity - genetics ; Male ; Middle Aged ; Mutation - genetics ; Oligodendroglioma - genetics ; Oligodendroglioma - pathology ; Stereotaxic Techniques ; Tumor Suppressor Protein p53 - genetics ; World Health Organization ; Young Adult</subject><ispartof>Journal of neuropathology and experimental neurology, 2009-11, Vol.68 (11), p.1219-1228</ispartof><rights>2009 American Association of Neuropathologists, Inc</rights><rights>Copyright Lippincott Williams & Wilkins Nov 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4941-f4fb8ec9b6012ad9fbb350178f0a12c03ce13729c2fd0f88586560a317c894583</citedby><cites>FETCH-LOGICAL-c4941-f4fb8ec9b6012ad9fbb350178f0a12c03ce13729c2fd0f88586560a317c894583</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19816195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thon, Niklas</creatorcontrib><creatorcontrib>Eigenbrod, Sabina</creatorcontrib><creatorcontrib>Grasbon-Frodl, Eva M</creatorcontrib><creatorcontrib>Ruiter, Michael</creatorcontrib><creatorcontrib>Mehrkens, Jan H</creatorcontrib><creatorcontrib>Kreth, Simone</creatorcontrib><creatorcontrib>Tonn, Jörg C</creatorcontrib><creatorcontrib>Kretzschmar, Hans A</creatorcontrib><creatorcontrib>Kreth, Friedrich W</creatorcontrib><title>Novel Molecular Stereotactic Biopsy Procedures Reveal Intratumoral Homogeneity of Loss of Heterozygosity of 1p/19q and TP53 Mutations in World Health Organization Grade II Gliomas</title><title>Journal of neuropathology and experimental neurology</title><addtitle>J Neuropathol Exp Neurol</addtitle><description>We report a molecular stereotactic biopsy technique that combines histopathologic diagnosis with small sample size-adjusted molecular genetic analysis of low-grade gliomas that are ineligible for tumor resection. Loss of heterozygosity (LOH) of 1p/19q and TP53 mutationswere analyzed in 1-mm tissue samples from 42 World Health Organization grade II gliomas (30 astrocytomas, 8 oligoastrocytomas, 4 oligodendrogliomas) using polymerase chain reaction-based microsatellite and sequence analysis. Alternating histological and molecular genetic evaluation within 1-mm steps at different sites within each tumor was performed to determine reproducibility of the results and the intratumoral distribution of the biomarkers. Multiple serial biopsies (range, 2-5 per tumor) taken from distinct intratumoral areas revealed concordant molecular genetic findings and homogeneous distribution of both biomarkers throughout 41 tumors. Contamination by nonneoplastic tissue could be recognized by corresponding histological evaluation and resulted in discordant LOH findings in 1 tumor. The frequency of LOH 1p/19q and TP53 mutations was consistent with the literature; these genetic alterations were found to be mutually exclusive. There was no biopsy-related morbidity. We conclude that determination of the LOH 1p/19q and TP53 status using this molecular stereotactic biopsy technique is safe and reliable in cases of unresectable gliomas.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Astrocytoma - genetics</subject><subject>Astrocytoma - pathology</subject><subject>Chromosomes, Human, Pair 1 - genetics</subject><subject>Chromosomes, Human, Pair 19 - genetics</subject><subject>Female</subject><subject>Glioma - genetics</subject><subject>Glioma - pathology</subject><subject>Humans</subject><subject>Loss of Heterozygosity - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation - genetics</subject><subject>Oligodendroglioma - genetics</subject><subject>Oligodendroglioma - pathology</subject><subject>Stereotaxic Techniques</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>World Health Organization</subject><subject>Young Adult</subject><issn>0022-3069</issn><issn>1554-6578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU9PGzEQxa2qVUlpv0FVWb1wCnjW-8c-togmkUJAlKrHldc7Dku962B7QeFr9QvWkEiVOHAajeb3nkbvEfIZ2DEwWZ2szlbHrGHAkYOABhEMvCETKIp8WhaVeEsmjGXZlLNSHpAPIdwyxiST-XtyAFJACbKYkL8rd4-WnjuLerTK058RPbqodOw0_d65TdjSS-80tqPHQK_wHpWliyF6Fcfe-bTMXe_WOGAXt9QZunQhPM05Jiv3uF27sL_A5gTkHVVDS68vC07Px6hi54ZAu4H-dt62SaRsvKEXfq2G7vH5SmdetUgXCzqznetV-EjeGWUDftrPQ_Lrx9n16Xy6vJgtTr8tpzqXOUxNbhqBWjYlg0y10jQNLxhUwjAFmWZcI_AqkzozLTNCFKIsSqY4VFrIvBD8kBztfDfe3Y0YYt13QaO1akA3hrriOaTsZZXIry_IWzf6IT1XZ5msgAuWJyjfQdqnhDyaeuO7XvltDax-qrROldYvK02yL3vvsemx_S_ad5gAsQMenE2Jhz92fEBf3zwn-br3P2mmshw</recordid><startdate>200911</startdate><enddate>200911</enddate><creator>Thon, Niklas</creator><creator>Eigenbrod, Sabina</creator><creator>Grasbon-Frodl, Eva M</creator><creator>Ruiter, Michael</creator><creator>Mehrkens, Jan H</creator><creator>Kreth, Simone</creator><creator>Tonn, Jörg C</creator><creator>Kretzschmar, Hans A</creator><creator>Kreth, Friedrich W</creator><general>American Association of Neuropathologists, Inc</general><general>Oxford University Press</general><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>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>200911</creationdate><title>Novel Molecular Stereotactic Biopsy Procedures Reveal Intratumoral Homogeneity of Loss of Heterozygosity of 1p/19q and TP53 Mutations in World Health Organization Grade II Gliomas</title><author>Thon, Niklas ; Eigenbrod, Sabina ; Grasbon-Frodl, Eva M ; Ruiter, Michael ; Mehrkens, Jan H ; Kreth, Simone ; Tonn, Jörg C ; Kretzschmar, Hans A ; Kreth, Friedrich W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4941-f4fb8ec9b6012ad9fbb350178f0a12c03ce13729c2fd0f88586560a317c894583</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Astrocytoma - genetics</topic><topic>Astrocytoma - pathology</topic><topic>Chromosomes, Human, Pair 1 - genetics</topic><topic>Chromosomes, Human, Pair 19 - genetics</topic><topic>Female</topic><topic>Glioma - genetics</topic><topic>Glioma - pathology</topic><topic>Humans</topic><topic>Loss of Heterozygosity - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation - genetics</topic><topic>Oligodendroglioma - genetics</topic><topic>Oligodendroglioma - pathology</topic><topic>Stereotaxic Techniques</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>World Health Organization</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Thon, Niklas</creatorcontrib><creatorcontrib>Eigenbrod, Sabina</creatorcontrib><creatorcontrib>Grasbon-Frodl, Eva M</creatorcontrib><creatorcontrib>Ruiter, Michael</creatorcontrib><creatorcontrib>Mehrkens, Jan H</creatorcontrib><creatorcontrib>Kreth, Simone</creatorcontrib><creatorcontrib>Tonn, Jörg C</creatorcontrib><creatorcontrib>Kretzschmar, Hans A</creatorcontrib><creatorcontrib>Kreth, Friedrich W</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><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>Thon, Niklas</au><au>Eigenbrod, Sabina</au><au>Grasbon-Frodl, Eva M</au><au>Ruiter, Michael</au><au>Mehrkens, Jan H</au><au>Kreth, Simone</au><au>Tonn, Jörg C</au><au>Kretzschmar, Hans A</au><au>Kreth, Friedrich W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel Molecular Stereotactic Biopsy Procedures Reveal Intratumoral Homogeneity of Loss of Heterozygosity of 1p/19q and TP53 Mutations in World Health Organization Grade II Gliomas</atitle><jtitle>Journal of neuropathology and experimental neurology</jtitle><addtitle>J Neuropathol Exp Neurol</addtitle><date>2009-11</date><risdate>2009</risdate><volume>68</volume><issue>11</issue><spage>1219</spage><epage>1228</epage><pages>1219-1228</pages><issn>0022-3069</issn><eissn>1554-6578</eissn><coden>JNENAD</coden><abstract>We report a molecular stereotactic biopsy technique that combines histopathologic diagnosis with small sample size-adjusted molecular genetic analysis of low-grade gliomas that are ineligible for tumor resection. Loss of heterozygosity (LOH) of 1p/19q and TP53 mutationswere analyzed in 1-mm tissue samples from 42 World Health Organization grade II gliomas (30 astrocytomas, 8 oligoastrocytomas, 4 oligodendrogliomas) using polymerase chain reaction-based microsatellite and sequence analysis. Alternating histological and molecular genetic evaluation within 1-mm steps at different sites within each tumor was performed to determine reproducibility of the results and the intratumoral distribution of the biomarkers. Multiple serial biopsies (range, 2-5 per tumor) taken from distinct intratumoral areas revealed concordant molecular genetic findings and homogeneous distribution of both biomarkers throughout 41 tumors. Contamination by nonneoplastic tissue could be recognized by corresponding histological evaluation and resulted in discordant LOH findings in 1 tumor. The frequency of LOH 1p/19q and TP53 mutations was consistent with the literature; these genetic alterations were found to be mutually exclusive. There was no biopsy-related morbidity. We conclude that determination of the LOH 1p/19q and TP53 status using this molecular stereotactic biopsy technique is safe and reliable in cases of unresectable gliomas.</abstract><cop>England</cop><pub>American Association of Neuropathologists, Inc</pub><pmid>19816195</pmid><doi>10.1097/NEN.0b013e3181bee1f1</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Astrocytoma - genetics Astrocytoma - pathology Chromosomes, Human, Pair 1 - genetics Chromosomes, Human, Pair 19 - genetics Female Glioma - genetics Glioma - pathology Humans Loss of Heterozygosity - genetics Male Middle Aged Mutation - genetics Oligodendroglioma - genetics Oligodendroglioma - pathology Stereotaxic Techniques Tumor Suppressor Protein p53 - genetics World Health Organization Young Adult |
| title | Novel Molecular Stereotactic Biopsy Procedures Reveal Intratumoral Homogeneity of Loss of Heterozygosity of 1p/19q and TP53 Mutations in World Health Organization Grade II Gliomas |
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