Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions

Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors—distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using a...

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Veröffentlicht in:Acta neuropathologica 2023-05, Vol.145 (5), p.667-680
Hauptverfasser: Bogumil, Henri, Sill, Martin, Schrimpf, Daniel, Ismer, Britta, Blume, Christina, Rahmanzade, Ramin, Hinz, Felix, Cherkezov, Asan, Banan, Rouzbeh, Friedel, Dennis, Reuss, David E., Selt, Florian, Ecker, Jonas, Milde, Till, Pajtler, Kristian W., Schittenhelm, Jens, Hench, Jürgen, Frank, Stephan, Boldt, Henning B., Kristensen, Bjarne Winther, Scheie, David, Melchior, Linea C., Olesen, Viola, Sehested, Astrid, Boué, Daniel R., Abdullaev, Zied, Satgunaseelan, Laveniya, Kurth, Ina, Seidlitz, Annekatrin, White, Christine L., Ng, Ho-Keung, Shi, Zhi-Feng, Haberler, Christine, Deckert, Martina, Timmer, Marco, Goldbrunner, Roland, Tauziède-Espariat, Arnault, Varlet, Pascale, Brandner, Sebastian, Alexandrescu, Sanda, Snuderl, Matija, Aldape, Kenneth, Korshunov, Andrey, Witt, Olaf, Herold-Mende, Christel, Unterberg, Andreas, Wick, Wolfgang, Pfister, Stefan M., von Deimling, Andreas, Jones, David T. W., Sahm, Felix, Sievers, Philipp
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container_end_page 680
container_issue 5
container_start_page 667
container_title Acta neuropathologica
container_volume 145
creator Bogumil, Henri
Sill, Martin
Schrimpf, Daniel
Ismer, Britta
Blume, Christina
Rahmanzade, Ramin
Hinz, Felix
Cherkezov, Asan
Banan, Rouzbeh
Friedel, Dennis
Reuss, David E.
Selt, Florian
Ecker, Jonas
Milde, Till
Pajtler, Kristian W.
Schittenhelm, Jens
Hench, Jürgen
Frank, Stephan
Boldt, Henning B.
Kristensen, Bjarne Winther
Scheie, David
Melchior, Linea C.
Olesen, Viola
Sehested, Astrid
Boué, Daniel R.
Abdullaev, Zied
Satgunaseelan, Laveniya
Kurth, Ina
Seidlitz, Annekatrin
White, Christine L.
Ng, Ho-Keung
Shi, Zhi-Feng
Haberler, Christine
Deckert, Martina
Timmer, Marco
Goldbrunner, Roland
Tauziède-Espariat, Arnault
Varlet, Pascale
Brandner, Sebastian
Alexandrescu, Sanda
Snuderl, Matija
Aldape, Kenneth
Korshunov, Andrey
Witt, Olaf
Herold-Mende, Christel
Unterberg, Andreas
Wick, Wolfgang
Pfister, Stefan M.
von Deimling, Andreas
Jones, David T. W.
Sahm, Felix
Sievers, Philipp
description Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors—distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors ( n  = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3 ) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited ( n  = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B . Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors.
doi_str_mv 10.1007/s00401-023-02558-0
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Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited ( n  = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B . Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors.</description><identifier>ISSN: 0001-6322</identifier><identifier>EISSN: 1432-0533</identifier><identifier>DOI: 10.1007/s00401-023-02558-0</identifier><identifier>PMID: 36933012</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Analysis ; Biomarkers, Tumor - genetics ; Brain - pathology ; Brain cancer ; Brain Neoplasms - genetics ; Brain Neoplasms - pathology ; Brain tumors ; Central Nervous System Neoplasms ; Copy number ; Diseases ; DNA methylation ; DNA sequencing ; Gene Fusion ; Genes ; Genetic research ; Humans ; Immunohistochemistry ; Medical colleges ; Medicine ; Medicine &amp; Public Health ; Methylation ; Microvasculature ; Neoplasms, Neuroepithelial - genetics ; Neoplasms, Neuroepithelial - pathology ; Neurosciences ; Nucleotide sequencing ; Original Paper ; Pathology ; Receptor Protein-Tyrosine Kinases - genetics ; Relapse ; Survival ; Tumors ; X-linked Nuclear Protein - genetics ; Young Adult</subject><ispartof>Acta neuropathologica, 2023-05, Vol.145 (5), p.667-680</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>COPYRIGHT 2023 Springer</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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W.</creatorcontrib><creatorcontrib>Sahm, Felix</creatorcontrib><creatorcontrib>Sievers, Philipp</creatorcontrib><title>Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions</title><title>Acta neuropathologica</title><addtitle>Acta Neuropathol</addtitle><addtitle>Acta Neuropathol</addtitle><description>Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors—distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors ( n  = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3 ) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited ( n  = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B . Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors.</description><subject>Analysis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Brain - pathology</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - pathology</subject><subject>Brain tumors</subject><subject>Central Nervous System Neoplasms</subject><subject>Copy number</subject><subject>Diseases</subject><subject>DNA methylation</subject><subject>DNA sequencing</subject><subject>Gene Fusion</subject><subject>Genes</subject><subject>Genetic research</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical colleges</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Methylation</subject><subject>Microvasculature</subject><subject>Neoplasms, Neuroepithelial - genetics</subject><subject>Neoplasms, Neuroepithelial - pathology</subject><subject>Neurosciences</subject><subject>Nucleotide sequencing</subject><subject>Original Paper</subject><subject>Pathology</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Relapse</subject><subject>Survival</subject><subject>Tumors</subject><subject>X-linked Nuclear Protein - genetics</subject><subject>Young Adult</subject><issn>0001-6322</issn><issn>1432-0533</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><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>eNp9kl1rFDEUhgdR7Fr9A15IwJsKTs3XTGZ7I0PRVVoUygrehUwms03NJGuSUfbf-FM92922VkRCCCfnOe_Jx1sUzwk-JhiLNwljjkmJKYNZVU2JHxQzwhktccXYw2KGMaRrRulB8SSlK4io4NXj4oDVc8YgmhW_Fs4Gb6YYvHIoT2OI6KfNl6hdXnxFymUTVQbiNfpmvUoGDVOCECnfw1Rrp1K2Gg1G5SmahI4Wy_asfXWCFBqDM3pyKroN6i1gXmfURWX9vk_erM2uWQQwRuMz-rS8OEMr428apafFo0G5ZJ7t18Piy_t3y9MP5fnnxcfT9rzUFae57LXu5wNnYl4PvaoaIkiNu0pwxjVRuuF1wzilXTd0Qmjea8p1z3p4rYE2DRbssHi7011P3Wh6DYeJysl1tKOKGxmUlfcz3l7KVfghCSZkTjkHhaO9QgzfJ5OyHG3SxjnlTZiSpA2uMK15vUVf_oVehSnCD1xTrG6EoOKOWilnpPVDgMZ6KypbATKckJoAdfwPCkZvRqvhbwcL-_cK6K5Ax5BSNMPtJQmWW2PJnbEkGEteG0tiKHrx5_Pcltw4CQC2AxKk_MrEuyv9R_Y3Fh_ZZw</recordid><startdate>20230501</startdate><enddate>20230501</enddate><creator>Bogumil, Henri</creator><creator>Sill, Martin</creator><creator>Schrimpf, Daniel</creator><creator>Ismer, Britta</creator><creator>Blume, Christina</creator><creator>Rahmanzade, Ramin</creator><creator>Hinz, Felix</creator><creator>Cherkezov, Asan</creator><creator>Banan, Rouzbeh</creator><creator>Friedel, Dennis</creator><creator>Reuss, David E.</creator><creator>Selt, Florian</creator><creator>Ecker, Jonas</creator><creator>Milde, Till</creator><creator>Pajtler, Kristian W.</creator><creator>Schittenhelm, Jens</creator><creator>Hench, Jürgen</creator><creator>Frank, Stephan</creator><creator>Boldt, Henning B.</creator><creator>Kristensen, Bjarne Winther</creator><creator>Scheie, David</creator><creator>Melchior, Linea C.</creator><creator>Olesen, Viola</creator><creator>Sehested, Astrid</creator><creator>Boué, Daniel R.</creator><creator>Abdullaev, Zied</creator><creator>Satgunaseelan, Laveniya</creator><creator>Kurth, Ina</creator><creator>Seidlitz, Annekatrin</creator><creator>White, Christine L.</creator><creator>Ng, Ho-Keung</creator><creator>Shi, Zhi-Feng</creator><creator>Haberler, Christine</creator><creator>Deckert, Martina</creator><creator>Timmer, Marco</creator><creator>Goldbrunner, Roland</creator><creator>Tauziède-Espariat, Arnault</creator><creator>Varlet, Pascale</creator><creator>Brandner, Sebastian</creator><creator>Alexandrescu, Sanda</creator><creator>Snuderl, Matija</creator><creator>Aldape, Kenneth</creator><creator>Korshunov, Andrey</creator><creator>Witt, Olaf</creator><creator>Herold-Mende, Christel</creator><creator>Unterberg, Andreas</creator><creator>Wick, Wolfgang</creator><creator>Pfister, Stefan M.</creator><creator>von Deimling, Andreas</creator><creator>Jones, David T. 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W. ; Sahm, Felix ; Sievers, Philipp</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c542t-dccd9f43796fda5817160b57434c1ac84683422bbfb77c4dc24cd3d143f288073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analysis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Brain - pathology</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain Neoplasms - pathology</topic><topic>Brain tumors</topic><topic>Central Nervous System Neoplasms</topic><topic>Copy number</topic><topic>Diseases</topic><topic>DNA methylation</topic><topic>DNA sequencing</topic><topic>Gene Fusion</topic><topic>Genes</topic><topic>Genetic research</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medical colleges</topic><topic>Medicine</topic><topic>Medicine &amp; Public Health</topic><topic>Methylation</topic><topic>Microvasculature</topic><topic>Neoplasms, Neuroepithelial - genetics</topic><topic>Neoplasms, Neuroepithelial - pathology</topic><topic>Neurosciences</topic><topic>Nucleotide sequencing</topic><topic>Original Paper</topic><topic>Pathology</topic><topic>Receptor Protein-Tyrosine Kinases - genetics</topic><topic>Relapse</topic><topic>Survival</topic><topic>Tumors</topic><topic>X-linked Nuclear Protein - genetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bogumil, Henri</creatorcontrib><creatorcontrib>Sill, Martin</creatorcontrib><creatorcontrib>Schrimpf, Daniel</creatorcontrib><creatorcontrib>Ismer, Britta</creatorcontrib><creatorcontrib>Blume, Christina</creatorcontrib><creatorcontrib>Rahmanzade, Ramin</creatorcontrib><creatorcontrib>Hinz, Felix</creatorcontrib><creatorcontrib>Cherkezov, Asan</creatorcontrib><creatorcontrib>Banan, Rouzbeh</creatorcontrib><creatorcontrib>Friedel, Dennis</creatorcontrib><creatorcontrib>Reuss, David E.</creatorcontrib><creatorcontrib>Selt, Florian</creatorcontrib><creatorcontrib>Ecker, Jonas</creatorcontrib><creatorcontrib>Milde, Till</creatorcontrib><creatorcontrib>Pajtler, Kristian W.</creatorcontrib><creatorcontrib>Schittenhelm, Jens</creatorcontrib><creatorcontrib>Hench, Jürgen</creatorcontrib><creatorcontrib>Frank, Stephan</creatorcontrib><creatorcontrib>Boldt, Henning B.</creatorcontrib><creatorcontrib>Kristensen, Bjarne Winther</creatorcontrib><creatorcontrib>Scheie, David</creatorcontrib><creatorcontrib>Melchior, Linea C.</creatorcontrib><creatorcontrib>Olesen, Viola</creatorcontrib><creatorcontrib>Sehested, Astrid</creatorcontrib><creatorcontrib>Boué, Daniel R.</creatorcontrib><creatorcontrib>Abdullaev, Zied</creatorcontrib><creatorcontrib>Satgunaseelan, Laveniya</creatorcontrib><creatorcontrib>Kurth, Ina</creatorcontrib><creatorcontrib>Seidlitz, Annekatrin</creatorcontrib><creatorcontrib>White, Christine L.</creatorcontrib><creatorcontrib>Ng, Ho-Keung</creatorcontrib><creatorcontrib>Shi, Zhi-Feng</creatorcontrib><creatorcontrib>Haberler, Christine</creatorcontrib><creatorcontrib>Deckert, Martina</creatorcontrib><creatorcontrib>Timmer, Marco</creatorcontrib><creatorcontrib>Goldbrunner, Roland</creatorcontrib><creatorcontrib>Tauziède-Espariat, Arnault</creatorcontrib><creatorcontrib>Varlet, Pascale</creatorcontrib><creatorcontrib>Brandner, Sebastian</creatorcontrib><creatorcontrib>Alexandrescu, Sanda</creatorcontrib><creatorcontrib>Snuderl, Matija</creatorcontrib><creatorcontrib>Aldape, Kenneth</creatorcontrib><creatorcontrib>Korshunov, Andrey</creatorcontrib><creatorcontrib>Witt, Olaf</creatorcontrib><creatorcontrib>Herold-Mende, Christel</creatorcontrib><creatorcontrib>Unterberg, Andreas</creatorcontrib><creatorcontrib>Wick, Wolfgang</creatorcontrib><creatorcontrib>Pfister, Stefan M.</creatorcontrib><creatorcontrib>von Deimling, Andreas</creatorcontrib><creatorcontrib>Jones, David T. W.</creatorcontrib><creatorcontrib>Sahm, Felix</creatorcontrib><creatorcontrib>Sievers, Philipp</creatorcontrib><collection>Springer Open Access</collection><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>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</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>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology Journals</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 One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta neuropathologica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bogumil, Henri</au><au>Sill, Martin</au><au>Schrimpf, Daniel</au><au>Ismer, Britta</au><au>Blume, Christina</au><au>Rahmanzade, Ramin</au><au>Hinz, Felix</au><au>Cherkezov, Asan</au><au>Banan, Rouzbeh</au><au>Friedel, Dennis</au><au>Reuss, David E.</au><au>Selt, Florian</au><au>Ecker, Jonas</au><au>Milde, Till</au><au>Pajtler, Kristian W.</au><au>Schittenhelm, Jens</au><au>Hench, Jürgen</au><au>Frank, Stephan</au><au>Boldt, Henning B.</au><au>Kristensen, Bjarne Winther</au><au>Scheie, David</au><au>Melchior, Linea C.</au><au>Olesen, Viola</au><au>Sehested, Astrid</au><au>Boué, Daniel R.</au><au>Abdullaev, Zied</au><au>Satgunaseelan, Laveniya</au><au>Kurth, Ina</au><au>Seidlitz, Annekatrin</au><au>White, Christine L.</au><au>Ng, Ho-Keung</au><au>Shi, Zhi-Feng</au><au>Haberler, Christine</au><au>Deckert, Martina</au><au>Timmer, Marco</au><au>Goldbrunner, Roland</au><au>Tauziède-Espariat, Arnault</au><au>Varlet, Pascale</au><au>Brandner, Sebastian</au><au>Alexandrescu, Sanda</au><au>Snuderl, Matija</au><au>Aldape, Kenneth</au><au>Korshunov, Andrey</au><au>Witt, Olaf</au><au>Herold-Mende, Christel</au><au>Unterberg, Andreas</au><au>Wick, Wolfgang</au><au>Pfister, Stefan M.</au><au>von Deimling, Andreas</au><au>Jones, David T. W.</au><au>Sahm, Felix</au><au>Sievers, Philipp</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions</atitle><jtitle>Acta neuropathologica</jtitle><stitle>Acta Neuropathol</stitle><addtitle>Acta Neuropathol</addtitle><date>2023-05-01</date><risdate>2023</risdate><volume>145</volume><issue>5</issue><spage>667</spage><epage>680</epage><pages>667-680</pages><issn>0001-6322</issn><eissn>1432-0533</eissn><abstract>Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors—distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors ( n  = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3 ) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited ( n  = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B . Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>36933012</pmid><doi>10.1007/s00401-023-02558-0</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-3237-6021</orcidid><oa>free_for_read</oa></addata></record>
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subjects Analysis
Biomarkers, Tumor - genetics
Brain - pathology
Brain cancer
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Brain tumors
Central Nervous System Neoplasms
Copy number
Diseases
DNA methylation
DNA sequencing
Gene Fusion
Genes
Genetic research
Humans
Immunohistochemistry
Medical colleges
Medicine
Medicine & Public Health
Methylation
Microvasculature
Neoplasms, Neuroepithelial - genetics
Neoplasms, Neuroepithelial - pathology
Neurosciences
Nucleotide sequencing
Original Paper
Pathology
Receptor Protein-Tyrosine Kinases - genetics
Relapse
Survival
Tumors
X-linked Nuclear Protein - genetics
Young Adult
title Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions
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