WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
Identifieur interne : 000053 ( Pmc/Checkpoint ); précédent : 000052; suivant : 000054WNT activation by lithium abrogates TP53 mutation associated radiation resistance in medulloblastoma
Auteurs : Nataliya Zhukova [Canada] ; Vijay Ramaswamy [Canada] ; Marc Remke [Canada] ; Dianna C. Martin ; Pedro Castelo-Branco [Portugal] ; Cindy H. Zhang ; Michael Fraser ; Ken Tse ; Raymond Poon ; David Jh Shih [Canada] ; Berivan Baskin [Suède] ; Peter N. Ray ; Eric Bouffet [Canada] ; Peter Dirks ; Andre O. Von Bueren [Allemagne] ; Elke Pfaff [Allemagne] ; Andrey Korshunov [Allemagne] ; David Tw Jones [Allemagne] ; Paul A. Northcott [Allemagne] ; Marcel Kool [Allemagne] ; Trevor J. Pugh [Canada] ; Scott L. Pomeroy [États-Unis] ; Yoon-Jae Cho [États-Unis] ; Torsten Pietsch [Allemagne] ; Marco Gessi [Allemagne] ; Stefan Rutkowski [Allemagne] ; Laszlo Bognár [Hongrie] ; Byung-Kyu Cho [Corée du Sud] ; Charles G. Eberhart [États-Unis] ; Cecile Faure Conter [France] ; Maryam Fouladi [États-Unis] ; Pim J. French [Pays-Bas] ; Wieslawa A. Grajkowska [Pologne] ; Nalin Gupta [États-Unis] ; Peter Hauser [Hongrie] ; Nada Jabado [Canada] ; Alexandre Vasiljevic [France] ; Shin Jung ; Seung-Ki Kim [Corée du Sud] ; Almos Klekner [Hongrie] ; Toshihiro Kumabe [Japon] ; Boleslaw Lach [Canada] ; Jeffrey R. Leonard [États-Unis] ; Linda M. Liau [États-Unis] ; Luca Massimi [Italie] ; Ian F. Pollack [États-Unis] ; Young Shin Ra [Corée du Sud] ; Joshua B. Rubin [États-Unis] ; Erwin G. Van Meir [États-Unis] ; Kyu-Chang Wang [Corée du Sud] ; William A. Weiss [États-Unis] ; Karel Zitterbart [République tchèque] ; Robert G. Bristow ; Benjamin Alman [Canada] ; Cynthia E. Hawkins ; David Malkin [Canada] ; Steven C. Clifford [Royaume-Uni] ; Stefan M. Pfister [Allemagne] ; Michael D. Taylor [Canada] ; Uri Tabori [Canada]Source :
- Acta Neuropathologica Communications [ 2051-5960 ] ; 2014.
Abstract
The online version of this article (doi:10.1186/s40478-014-0174-y) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s40478-014-0174-y
PubMed: 25539912
PubMed Central: 4297452
Affiliations:
- Allemagne, Canada, Corée du Sud, France, Hongrie, Italie, Japon, Pays-Bas, Pologne, Portugal, Royaume-Uni, République tchèque, Suède, États-Unis
- Auvergne-Rhône-Alpes, Bade-Wurtemberg, Californie, District de Cologne, District de Karlsruhe, East Middle Sweden, Géorgie (États-Unis), Hambourg, Hollande-Méridionale, Hongrie centrale, Latium, Maryland, Massachusetts, Missouri (État), Moravie, Ohio, Ontario, Pennsylvanie, Québec, Rhénanie-du-Nord-Westphalie, Rhône-Alpes, Région capitale de Séoul, Svealand
- Bonn, Brno, Budapest, Hambourg, Hamilton (Ontario), Heidelberg, Lyon, Montréal, Rome, Rotterdam, Séoul, Toronto, Uppsala
- Université McGill, Université McMaster, Université d'Uppsala, Université de Toronto
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PMC:4297452Le document en format XML
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mutation associated radiation resistance in medulloblastoma</title>
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<author><name sortKey="Castelo Branco, Pedro" sort="Castelo Branco, Pedro" uniqKey="Castelo Branco P" first="Pedro" last="Castelo-Branco">Pedro Castelo-Branco</name>
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<affiliation wicri:level="1"><nlm:aff id="Aff49">Departamento de Ciências Biomédicas e Medicina, Regenerative Medicine Program, Universidade do Algarve, 8005-139 Faro, Portugal</nlm:aff>
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<author><name sortKey="Zhang, Cindy H" sort="Zhang, Cindy H" uniqKey="Zhang C" first="Cindy H" last="Zhang">Cindy H. Zhang</name>
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<author><name sortKey="Fraser, Michael" sort="Fraser, Michael" uniqKey="Fraser M" first="Michael" last="Fraser">Michael Fraser</name>
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<author><name sortKey="Tse, Ken" sort="Tse, Ken" uniqKey="Tse K" first="Ken" last="Tse">Ken Tse</name>
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<author><name sortKey="Poon, Raymond" sort="Poon, Raymond" uniqKey="Poon R" first="Raymond" last="Poon">Raymond Poon</name>
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<author><name sortKey="Shih, David Jh" sort="Shih, David Jh" uniqKey="Shih D" first="David Jh" last="Shih">David Jh Shih</name>
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<affiliation><nlm:aff id="Aff3">Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
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<affiliation wicri:level="4"><nlm:aff id="Aff4">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada</nlm:aff>
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<author><name sortKey="Baskin, Berivan" sort="Baskin, Berivan" uniqKey="Baskin B" first="Berivan" last="Baskin">Berivan Baskin</name>
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<author><name sortKey="Ray, Peter N" sort="Ray, Peter N" uniqKey="Ray P" first="Peter N" last="Ray">Peter N. Ray</name>
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<author><name sortKey="Bouffet, Eric" sort="Bouffet, Eric" uniqKey="Bouffet E" first="Eric" last="Bouffet">Eric Bouffet</name>
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<author><name sortKey="Dirks, Peter" sort="Dirks, Peter" uniqKey="Dirks P" first="Peter" last="Dirks">Peter Dirks</name>
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<affiliation><nlm:aff id="Aff3">Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
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</affiliation>
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<author><name sortKey="Von Bueren, Andre O" sort="Von Bueren, Andre O" uniqKey="Von Bueren A" first="Andre O" last="Von Bueren">Andre O. Von Bueren</name>
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<affiliation wicri:level="3"><nlm:aff id="Aff14">Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg, Germany</nlm:aff>
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<wicri:regionArea>Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg</wicri:regionArea>
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<author><name sortKey="Korshunov, Andrey" sort="Korshunov, Andrey" uniqKey="Korshunov A" first="Andrey" last="Korshunov">Andrey Korshunov</name>
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<author><name sortKey="Jones, David Tw" sort="Jones, David Tw" uniqKey="Jones D" first="David Tw" last="Jones">David Tw Jones</name>
<affiliation wicri:level="3"><nlm:aff id="Aff13">Division of Molecular Genetics, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Genetics, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
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<affiliation wicri:level="3"><nlm:aff id="Aff14">Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
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<author><name sortKey="Northcott, Paul A" sort="Northcott, Paul A" uniqKey="Northcott P" first="Paul A" last="Northcott">Paul A. Northcott</name>
<affiliation wicri:level="3"><nlm:aff id="Aff13">Division of Molecular Genetics, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Genetics, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
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</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff14">Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
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</affiliation>
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<author><name sortKey="Kool, Marcel" sort="Kool, Marcel" uniqKey="Kool M" first="Marcel" last="Kool">Marcel Kool</name>
<affiliation wicri:level="3"><nlm:aff id="Aff13">Division of Molecular Genetics, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
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</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff14">Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pugh, Trevor J" sort="Pugh, Trevor J" uniqKey="Pugh T" first="Trevor J" last="Pugh">Trevor J. Pugh</name>
<affiliation><nlm:aff id="Aff16">Princess Margaret Cancer Centre, University Health Network, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff51">Department of Medical Biophysics, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pomeroy, Scott L" sort="Pomeroy, Scott L" uniqKey="Pomeroy S" first="Scott L" last="Pomeroy">Scott L. Pomeroy</name>
<affiliation wicri:level="2"><nlm:aff id="Aff17">Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Cho, Yoon Jae" sort="Cho, Yoon Jae" uniqKey="Cho Y" first="Yoon-Jae" last="Cho">Yoon-Jae Cho</name>
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<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Neurology, Stanford University, San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Pietsch, Torsten" sort="Pietsch, Torsten" uniqKey="Pietsch T" first="Torsten" last="Pietsch">Torsten Pietsch</name>
<affiliation wicri:level="3"><nlm:aff id="Aff19">Institute of Neuropathology, University of Bonn Medical Centre, Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Neuropathology, University of Bonn Medical Centre, Bonn</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Gessi, Marco" sort="Gessi, Marco" uniqKey="Gessi M" first="Marco" last="Gessi">Marco Gessi</name>
<affiliation wicri:level="3"><nlm:aff id="Aff19">Institute of Neuropathology, University of Bonn Medical Centre, Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Neuropathology, University of Bonn Medical Centre, Bonn</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rutkowski, Stefan" sort="Rutkowski, Stefan" uniqKey="Rutkowski S" first="Stefan" last="Rutkowski">Stefan Rutkowski</name>
<affiliation wicri:level="3"><nlm:aff id="Aff20">Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg</wicri:regionArea>
<placeName><settlement type="city">Hambourg</settlement>
<region type="land" nuts="2">Hambourg</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bognar, Laszlo" sort="Bognar, Laszlo" uniqKey="Bognar L" first="Laszlo" last="Bognár">Laszlo Bognár</name>
<affiliation wicri:level="1"><nlm:aff id="Aff21">Department of Neurosurgery, University of Debrecen, Clinical Centre, Debrecen, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea>Department of Neurosurgery, University of Debrecen, Clinical Centre, Debrecen</wicri:regionArea>
<wicri:noRegion>Debrecen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cho, Byung Kyu" sort="Cho, Byung Kyu" uniqKey="Cho B" first="Byung-Kyu" last="Cho">Byung-Kyu Cho</name>
<affiliation wicri:level="3"><nlm:aff id="Aff22">Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul, South Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Eberhart, Charles G" sort="Eberhart, Charles G" uniqKey="Eberhart C" first="Charles G" last="Eberhart">Charles G. Eberhart</name>
<affiliation wicri:level="2"><nlm:aff id="Aff23">Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Baltimore, MD USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Conter, Cecile Faure" sort="Conter, Cecile Faure" uniqKey="Conter C" first="Cecile Faure" last="Conter">Cecile Faure Conter</name>
<affiliation wicri:level="3"><nlm:aff id="Aff24">Department of Paediatrics, Institute of Hematology and Pediatric Oncology, Lyon, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Paediatrics, Institute of Hematology and Pediatric Oncology, Lyon</wicri:regionArea>
<placeName><region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fouladi, Maryam" sort="Fouladi, Maryam" uniqKey="Fouladi M" first="Maryam" last="Fouladi">Maryam Fouladi</name>
<affiliation wicri:level="2"><nlm:aff id="Aff25">Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Ohio</region>
</placeName>
<wicri:cityArea>Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="French, Pim J" sort="French, Pim J" uniqKey="French P" first="Pim J" last="French">Pim J. French</name>
<affiliation wicri:level="3"><nlm:aff id="Aff26">Department of Pathology and Neurology, Erasmus Medical Center, Rotterdam, Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pathology and Neurology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Grajkowska, Wieslawa A" sort="Grajkowska, Wieslawa A" uniqKey="Grajkowska W" first="Wieslawa A" last="Grajkowska">Wieslawa A. Grajkowska</name>
<affiliation wicri:level="1"><nlm:aff id="Aff27">Department of Pathology, The Children’s Memorial Health Institute, Warsaw, Poland</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea>Department of Pathology, The Children’s Memorial Health Institute, Warsaw</wicri:regionArea>
<wicri:noRegion>Warsaw</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gupta, Nalin" sort="Gupta, Nalin" uniqKey="Gupta N" first="Nalin" last="Gupta">Nalin Gupta</name>
<affiliation wicri:level="2"><nlm:aff id="Aff28">Departments of Neurological Surgery, University of California San Francisco, San Francisco, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Departments of Neurological Surgery, University of California San Francisco, San Francisco</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff29">Department of Pediatrics, University of California San Francisco, San Francisco, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Pediatrics, University of California San Francisco, San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hauser, Peter" sort="Hauser, Peter" uniqKey="Hauser P" first="Peter" last="Hauser">Peter Hauser</name>
<affiliation wicri:level="3"><nlm:aff id="Aff30">Department of Pediatrics, Semmelweis University, Budapest, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea>Department of Pediatrics, Semmelweis University, Budapest</wicri:regionArea>
<placeName><settlement type="city">Budapest</settlement>
<region nuts="2">Hongrie centrale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jabado, Nada" sort="Jabado, Nada" uniqKey="Jabado N" first="Nada" last="Jabado">Nada Jabado</name>
<affiliation wicri:level="4"><nlm:aff id="Aff31">Department of Pediatrics, Division of Haemato-Oncology, McGill University, Montreal, QC Canada</nlm:aff>
<orgName type="university">Université McGill</orgName>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vasiljevic, Alexandre" sort="Vasiljevic, Alexandre" uniqKey="Vasiljevic A" first="Alexandre" last="Vasiljevic">Alexandre Vasiljevic</name>
<affiliation wicri:level="1"><nlm:aff id="Aff32">Centre de Pathologie EST, Groupement Hospitalier EST, Hospices Civils de Lyon, Bron, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre de Pathologie EST, Groupement Hospitalier EST, Hospices Civils de Lyon, Bron</wicri:regionArea>
<wicri:noRegion>Bron</wicri:noRegion>
<wicri:noRegion>Bron</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jung, Shin" sort="Jung, Shin" uniqKey="Jung S" first="Shin" last="Jung">Shin Jung</name>
<affiliation><nlm:aff id="Aff33">Department of Neurosurgery, Université Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Chonnam South Korea</nlm:aff>
<wicri:noCountry code="subfield">Chonnam South Korea</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Kim, Seung Ki" sort="Kim, Seung Ki" uniqKey="Kim S" first="Seung-Ki" last="Kim">Seung-Ki Kim</name>
<affiliation wicri:level="3"><nlm:aff id="Aff22">Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul, South Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Klekner, Almos" sort="Klekner, Almos" uniqKey="Klekner A" first="Almos" last="Klekner">Almos Klekner</name>
<affiliation wicri:level="1"><nlm:aff id="Aff21">Department of Neurosurgery, University of Debrecen, Clinical Centre, Debrecen, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea>Department of Neurosurgery, University of Debrecen, Clinical Centre, Debrecen</wicri:regionArea>
<wicri:noRegion>Debrecen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kumabe, Toshihiro" sort="Kumabe, Toshihiro" uniqKey="Kumabe T" first="Toshihiro" last="Kumabe">Toshihiro Kumabe</name>
<affiliation wicri:level="1"><nlm:aff id="Aff34">Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai</wicri:regionArea>
<wicri:noRegion>Sendai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lach, Boleslaw" sort="Lach, Boleslaw" uniqKey="Lach B" first="Boleslaw" last="Lach">Boleslaw Lach</name>
<affiliation wicri:level="4"><nlm:aff id="Aff35">Department of Pathology and Molecular Medicine, Division of Anatomical Pathology, McMaster University, Hamilton, ON Canada</nlm:aff>
<orgName type="university">Université McMaster</orgName>
<country>Canada</country>
<placeName><settlement type="city">Hamilton (Ontario)</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Leonard, Jeffrey R" sort="Leonard, Jeffrey R" uniqKey="Leonard J" first="Jeffrey R" last="Leonard">Jeffrey R. Leonard</name>
<affiliation wicri:level="2"><nlm:aff id="Aff36">Department of Neurosurgery, Division of Pediatric Neurosurgery, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, MO USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Department of Neurosurgery, Division of Pediatric Neurosurgery, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Liau, Linda M" sort="Liau, Linda M" uniqKey="Liau L" first="Linda M" last="Liau">Linda M. Liau</name>
<affiliation wicri:level="2"><nlm:aff id="Aff38">Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Massimi, Luca" sort="Massimi, Luca" uniqKey="Massimi L" first="Luca" last="Massimi">Luca Massimi</name>
<affiliation wicri:level="3"><nlm:aff id="Aff39">Pediatric Neurosurgery, Catholic University Medical School, Rome, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Pediatric Neurosurgery, Catholic University Medical School, Rome</wicri:regionArea>
<placeName><settlement type="city">Rome</settlement>
<region nuts="2">Latium</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pollack, Ian F" sort="Pollack, Ian F" uniqKey="Pollack I" first="Ian F" last="Pollack">Ian F. Pollack</name>
<affiliation wicri:level="2"><nlm:aff id="Aff40">Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ra, Young Shin" sort="Ra, Young Shin" uniqKey="Ra Y" first="Young Shin" last="Ra">Young Shin Ra</name>
<affiliation wicri:level="3"><nlm:aff id="Aff41">Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul, South Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rubin, Joshua B" sort="Rubin, Joshua B" uniqKey="Rubin J" first="Joshua B" last="Rubin">Joshua B. Rubin</name>
<affiliation wicri:level="2"><nlm:aff id="Aff37">Department of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, MO USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Department of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Van Meir, Erwin G" sort="Van Meir, Erwin G" uniqKey="Van Meir E" first="Erwin G" last="Van Meir">Erwin G. Van Meir</name>
<affiliation wicri:level="2"><nlm:aff id="Aff42">Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
<wicri:cityArea>Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff43">Department of Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
<wicri:cityArea>Department of Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Wang, Kyu Chang" sort="Wang, Kyu Chang" uniqKey="Wang K" first="Kyu-Chang" last="Wang">Kyu-Chang Wang</name>
<affiliation wicri:level="3"><nlm:aff id="Aff22">Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul, South Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Weiss, William A" sort="Weiss, William A" uniqKey="Weiss W" first="William A" last="Weiss">William A. Weiss</name>
<affiliation wicri:level="2"><nlm:aff id="Aff44">Department of Neurological Surgery, University of California San Francisco, San Francisco, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Neurological Surgery, University of California San Francisco, San Francisco</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff45">Department of Paediatrics, University of California San Francisco, San Francisco, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Paediatrics, University of California San Francisco, San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Zitterbart, Karel" sort="Zitterbart, Karel" uniqKey="Zitterbart K" first="Karel" last="Zitterbart">Karel Zitterbart</name>
<affiliation wicri:level="3"><nlm:aff id="Aff46">Department of Pediatric Oncology, University Hospital Brno and Masaryk University School of Medicine, Brno, Czech Republic and Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic</nlm:aff>
<country xml:lang="fr">République tchèque</country>
<wicri:regionArea>Department of Pediatric Oncology, University Hospital Brno and Masaryk University School of Medicine, Brno, Czech Republic and Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno</wicri:regionArea>
<placeName><settlement type="city">Brno</settlement>
<region>Moravie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bristow, Robert G" sort="Bristow, Robert G" uniqKey="Bristow R" first="Robert G" last="Bristow">Robert G. Bristow</name>
<affiliation><nlm:aff id="Aff6">Cellular Imaging Core, STTARR Innovation Facility/Radiation Medicine Program and Department of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Alman, Benjamin" sort="Alman, Benjamin" uniqKey="Alman B" first="Benjamin" last="Alman">Benjamin Alman</name>
<affiliation><nlm:aff id="Aff7">Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff8">Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="Aff9">Division of Orthopedic Surgery, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff10">Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hawkins, Cynthia E" sort="Hawkins, Cynthia E" uniqKey="Hawkins C" first="Cynthia E" last="Hawkins">Cynthia E. Hawkins</name>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff5">Division of Pathology, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Malkin, David" sort="Malkin, David" uniqKey="Malkin D" first="David" last="Malkin">David Malkin</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, 555 University Avenue, M5G 1X8 Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff8">Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="Aff47">Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Clifford, Steven C" sort="Clifford, Steven C" uniqKey="Clifford S" first="Steven C" last="Clifford">Steven C. Clifford</name>
<affiliation wicri:level="1"><nlm:aff id="Aff48">Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle-upon-Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pfister, Stefan M" sort="Pfister, Stefan M" uniqKey="Pfister S" first="Stefan M" last="Pfister">Stefan M. Pfister</name>
<affiliation wicri:level="3"><nlm:aff id="Aff13">Division of Molecular Genetics, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Genetics, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff14">Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Taylor, Michael D" sort="Taylor, Michael D" uniqKey="Taylor M" first="Michael D" last="Taylor">Michael D. Taylor</name>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff3">Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff4">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tabori, Uri" sort="Tabori, Uri" uniqKey="Tabori U" first="Uri" last="Tabori">Uri Tabori</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, 555 University Avenue, M5G 1X8 Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
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<idno type="pmid">25539912</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">WNT activation by lithium abrogates <italic>TP53</italic>
mutation associated radiation resistance in medulloblastoma</title>
<author><name sortKey="Zhukova, Nataliya" sort="Zhukova, Nataliya" uniqKey="Zhukova N" first="Nataliya" last="Zhukova">Nataliya Zhukova</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, 555 University Avenue, M5G 1X8 Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Ramaswamy, Vijay" sort="Ramaswamy, Vijay" uniqKey="Ramaswamy V" first="Vijay" last="Ramaswamy">Vijay Ramaswamy</name>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff3">Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff4">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Remke, Marc" sort="Remke, Marc" uniqKey="Remke M" first="Marc" last="Remke">Marc Remke</name>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff3">Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff4">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Martin, Dianna C" sort="Martin, Dianna C" uniqKey="Martin D" first="Dianna C" last="Martin">Dianna C. Martin</name>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Castelo Branco, Pedro" sort="Castelo Branco, Pedro" uniqKey="Castelo Branco P" first="Pedro" last="Castelo-Branco">Pedro Castelo-Branco</name>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff49">Departamento de Ciências Biomédicas e Medicina, Regenerative Medicine Program, Universidade do Algarve, 8005-139 Faro, Portugal</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Departamento de Ciências Biomédicas e Medicina, Regenerative Medicine Program, Universidade do Algarve, 8005-139 Faro</wicri:regionArea>
<wicri:noRegion>8005-139 Faro</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff50">Centre for Molecular and Structural Biomedicine, CBME/IBB, LA. University of Algarve, 8005-139 Faro, Portugal</nlm:aff>
<country xml:lang="fr">Portugal</country>
<wicri:regionArea>Centre for Molecular and Structural Biomedicine, CBME/IBB, LA. University of Algarve, 8005-139 Faro</wicri:regionArea>
<wicri:noRegion>8005-139 Faro</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhang, Cindy H" sort="Zhang, Cindy H" uniqKey="Zhang C" first="Cindy H" last="Zhang">Cindy H. Zhang</name>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Fraser, Michael" sort="Fraser, Michael" uniqKey="Fraser M" first="Michael" last="Fraser">Michael Fraser</name>
<affiliation><nlm:aff id="Aff6">Cellular Imaging Core, STTARR Innovation Facility/Radiation Medicine Program and Department of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Tse, Ken" sort="Tse, Ken" uniqKey="Tse K" first="Ken" last="Tse">Ken Tse</name>
<affiliation><nlm:aff id="Aff6">Cellular Imaging Core, STTARR Innovation Facility/Radiation Medicine Program and Department of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Poon, Raymond" sort="Poon, Raymond" uniqKey="Poon R" first="Raymond" last="Poon">Raymond Poon</name>
<affiliation><nlm:aff id="Aff7">Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Shih, David Jh" sort="Shih, David Jh" uniqKey="Shih D" first="David Jh" last="Shih">David Jh Shih</name>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff3">Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff4">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Baskin, Berivan" sort="Baskin, Berivan" uniqKey="Baskin B" first="Berivan" last="Baskin">Berivan Baskin</name>
<affiliation wicri:level="4"><nlm:aff id="Aff52">Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala</wicri:regionArea>
<orgName type="university">Université d'Uppsala</orgName>
<placeName><settlement type="city">Uppsala</settlement>
<region nuts="1">Svealand</region>
<region nuts="1">East Middle Sweden</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff53">Department of Clinical Genetics, Uppsala University Hospital, Uppsala, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Genetics, Uppsala University Hospital, Uppsala</wicri:regionArea>
<wicri:noRegion>Uppsala</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ray, Peter N" sort="Ray, Peter N" uniqKey="Ray P" first="Peter N" last="Ray">Peter N. Ray</name>
<affiliation><nlm:aff id="Aff11">Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Bouffet, Eric" sort="Bouffet, Eric" uniqKey="Bouffet E" first="Eric" last="Bouffet">Eric Bouffet</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, 555 University Avenue, M5G 1X8 Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dirks, Peter" sort="Dirks, Peter" uniqKey="Dirks P" first="Peter" last="Dirks">Peter Dirks</name>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff3">Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Von Bueren, Andre O" sort="Von Bueren, Andre O" uniqKey="Von Bueren A" first="Andre O" last="Von Bueren">Andre O. Von Bueren</name>
<affiliation wicri:level="1"><nlm:aff id="Aff12">Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology University Medical Center, Gottingen, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology University Medical Center, Gottingen</wicri:regionArea>
<wicri:noRegion>Gottingen</wicri:noRegion>
<wicri:noRegion>Gottingen</wicri:noRegion>
<wicri:noRegion>Gottingen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff20">Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg</wicri:regionArea>
<placeName><settlement type="city">Hambourg</settlement>
<region type="land" nuts="2">Hambourg</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pfaff, Elke" sort="Pfaff, Elke" uniqKey="Pfaff E" first="Elke" last="Pfaff">Elke Pfaff</name>
<affiliation wicri:level="3"><nlm:aff id="Aff13">Division of Molecular Genetics, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Genetics, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff14">Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Korshunov, Andrey" sort="Korshunov, Andrey" uniqKey="Korshunov A" first="Andrey" last="Korshunov">Andrey Korshunov</name>
<affiliation wicri:level="3"><nlm:aff id="Aff15">CCU Neuropathology, DKFZ and Department of Neuropathology, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>CCU Neuropathology, DKFZ and Department of Neuropathology, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jones, David Tw" sort="Jones, David Tw" uniqKey="Jones D" first="David Tw" last="Jones">David Tw Jones</name>
<affiliation wicri:level="3"><nlm:aff id="Aff13">Division of Molecular Genetics, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Genetics, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff14">Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Northcott, Paul A" sort="Northcott, Paul A" uniqKey="Northcott P" first="Paul A" last="Northcott">Paul A. Northcott</name>
<affiliation wicri:level="3"><nlm:aff id="Aff13">Division of Molecular Genetics, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Genetics, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff14">Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kool, Marcel" sort="Kool, Marcel" uniqKey="Kool M" first="Marcel" last="Kool">Marcel Kool</name>
<affiliation wicri:level="3"><nlm:aff id="Aff13">Division of Molecular Genetics, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Genetics, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff14">Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pugh, Trevor J" sort="Pugh, Trevor J" uniqKey="Pugh T" first="Trevor J" last="Pugh">Trevor J. Pugh</name>
<affiliation><nlm:aff id="Aff16">Princess Margaret Cancer Centre, University Health Network, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff51">Department of Medical Biophysics, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pomeroy, Scott L" sort="Pomeroy, Scott L" uniqKey="Pomeroy S" first="Scott L" last="Pomeroy">Scott L. Pomeroy</name>
<affiliation wicri:level="2"><nlm:aff id="Aff17">Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Cho, Yoon Jae" sort="Cho, Yoon Jae" uniqKey="Cho Y" first="Yoon-Jae" last="Cho">Yoon-Jae Cho</name>
<affiliation wicri:level="2"><nlm:aff id="Aff18">Department of Neurology, Stanford University, San Francisco, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Neurology, Stanford University, San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Pietsch, Torsten" sort="Pietsch, Torsten" uniqKey="Pietsch T" first="Torsten" last="Pietsch">Torsten Pietsch</name>
<affiliation wicri:level="3"><nlm:aff id="Aff19">Institute of Neuropathology, University of Bonn Medical Centre, Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Neuropathology, University of Bonn Medical Centre, Bonn</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gessi, Marco" sort="Gessi, Marco" uniqKey="Gessi M" first="Marco" last="Gessi">Marco Gessi</name>
<affiliation wicri:level="3"><nlm:aff id="Aff19">Institute of Neuropathology, University of Bonn Medical Centre, Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Neuropathology, University of Bonn Medical Centre, Bonn</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rutkowski, Stefan" sort="Rutkowski, Stefan" uniqKey="Rutkowski S" first="Stefan" last="Rutkowski">Stefan Rutkowski</name>
<affiliation wicri:level="3"><nlm:aff id="Aff20">Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg</wicri:regionArea>
<placeName><settlement type="city">Hambourg</settlement>
<region type="land" nuts="2">Hambourg</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bognar, Laszlo" sort="Bognar, Laszlo" uniqKey="Bognar L" first="Laszlo" last="Bognár">Laszlo Bognár</name>
<affiliation wicri:level="1"><nlm:aff id="Aff21">Department of Neurosurgery, University of Debrecen, Clinical Centre, Debrecen, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea>Department of Neurosurgery, University of Debrecen, Clinical Centre, Debrecen</wicri:regionArea>
<wicri:noRegion>Debrecen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cho, Byung Kyu" sort="Cho, Byung Kyu" uniqKey="Cho B" first="Byung-Kyu" last="Cho">Byung-Kyu Cho</name>
<affiliation wicri:level="3"><nlm:aff id="Aff22">Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul, South Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Eberhart, Charles G" sort="Eberhart, Charles G" uniqKey="Eberhart C" first="Charles G" last="Eberhart">Charles G. Eberhart</name>
<affiliation wicri:level="2"><nlm:aff id="Aff23">Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Baltimore, MD USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Maryland</region>
</placeName>
<wicri:cityArea>Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Baltimore</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Conter, Cecile Faure" sort="Conter, Cecile Faure" uniqKey="Conter C" first="Cecile Faure" last="Conter">Cecile Faure Conter</name>
<affiliation wicri:level="3"><nlm:aff id="Aff24">Department of Paediatrics, Institute of Hematology and Pediatric Oncology, Lyon, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Paediatrics, Institute of Hematology and Pediatric Oncology, Lyon</wicri:regionArea>
<placeName><region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fouladi, Maryam" sort="Fouladi, Maryam" uniqKey="Fouladi M" first="Maryam" last="Fouladi">Maryam Fouladi</name>
<affiliation wicri:level="2"><nlm:aff id="Aff25">Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Ohio</region>
</placeName>
<wicri:cityArea>Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="French, Pim J" sort="French, Pim J" uniqKey="French P" first="Pim J" last="French">Pim J. French</name>
<affiliation wicri:level="3"><nlm:aff id="Aff26">Department of Pathology and Neurology, Erasmus Medical Center, Rotterdam, Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pathology and Neurology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Grajkowska, Wieslawa A" sort="Grajkowska, Wieslawa A" uniqKey="Grajkowska W" first="Wieslawa A" last="Grajkowska">Wieslawa A. Grajkowska</name>
<affiliation wicri:level="1"><nlm:aff id="Aff27">Department of Pathology, The Children’s Memorial Health Institute, Warsaw, Poland</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea>Department of Pathology, The Children’s Memorial Health Institute, Warsaw</wicri:regionArea>
<wicri:noRegion>Warsaw</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gupta, Nalin" sort="Gupta, Nalin" uniqKey="Gupta N" first="Nalin" last="Gupta">Nalin Gupta</name>
<affiliation wicri:level="2"><nlm:aff id="Aff28">Departments of Neurological Surgery, University of California San Francisco, San Francisco, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Departments of Neurological Surgery, University of California San Francisco, San Francisco</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff29">Department of Pediatrics, University of California San Francisco, San Francisco, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Pediatrics, University of California San Francisco, San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Hauser, Peter" sort="Hauser, Peter" uniqKey="Hauser P" first="Peter" last="Hauser">Peter Hauser</name>
<affiliation wicri:level="3"><nlm:aff id="Aff30">Department of Pediatrics, Semmelweis University, Budapest, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea>Department of Pediatrics, Semmelweis University, Budapest</wicri:regionArea>
<placeName><settlement type="city">Budapest</settlement>
<region nuts="2">Hongrie centrale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jabado, Nada" sort="Jabado, Nada" uniqKey="Jabado N" first="Nada" last="Jabado">Nada Jabado</name>
<affiliation wicri:level="4"><nlm:aff id="Aff31">Department of Pediatrics, Division of Haemato-Oncology, McGill University, Montreal, QC Canada</nlm:aff>
<orgName type="university">Université McGill</orgName>
<country>Canada</country>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vasiljevic, Alexandre" sort="Vasiljevic, Alexandre" uniqKey="Vasiljevic A" first="Alexandre" last="Vasiljevic">Alexandre Vasiljevic</name>
<affiliation wicri:level="1"><nlm:aff id="Aff32">Centre de Pathologie EST, Groupement Hospitalier EST, Hospices Civils de Lyon, Bron, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre de Pathologie EST, Groupement Hospitalier EST, Hospices Civils de Lyon, Bron</wicri:regionArea>
<wicri:noRegion>Bron</wicri:noRegion>
<wicri:noRegion>Bron</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Jung, Shin" sort="Jung, Shin" uniqKey="Jung S" first="Shin" last="Jung">Shin Jung</name>
<affiliation><nlm:aff id="Aff33">Department of Neurosurgery, Université Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Chonnam South Korea</nlm:aff>
<wicri:noCountry code="subfield">Chonnam South Korea</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Kim, Seung Ki" sort="Kim, Seung Ki" uniqKey="Kim S" first="Seung-Ki" last="Kim">Seung-Ki Kim</name>
<affiliation wicri:level="3"><nlm:aff id="Aff22">Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul, South Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Klekner, Almos" sort="Klekner, Almos" uniqKey="Klekner A" first="Almos" last="Klekner">Almos Klekner</name>
<affiliation wicri:level="1"><nlm:aff id="Aff21">Department of Neurosurgery, University of Debrecen, Clinical Centre, Debrecen, Hungary</nlm:aff>
<country xml:lang="fr">Hongrie</country>
<wicri:regionArea>Department of Neurosurgery, University of Debrecen, Clinical Centre, Debrecen</wicri:regionArea>
<wicri:noRegion>Debrecen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kumabe, Toshihiro" sort="Kumabe, Toshihiro" uniqKey="Kumabe T" first="Toshihiro" last="Kumabe">Toshihiro Kumabe</name>
<affiliation wicri:level="1"><nlm:aff id="Aff34">Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan</nlm:aff>
<country xml:lang="fr">Japon</country>
<wicri:regionArea>Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai</wicri:regionArea>
<wicri:noRegion>Sendai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lach, Boleslaw" sort="Lach, Boleslaw" uniqKey="Lach B" first="Boleslaw" last="Lach">Boleslaw Lach</name>
<affiliation wicri:level="4"><nlm:aff id="Aff35">Department of Pathology and Molecular Medicine, Division of Anatomical Pathology, McMaster University, Hamilton, ON Canada</nlm:aff>
<orgName type="university">Université McMaster</orgName>
<country>Canada</country>
<placeName><settlement type="city">Hamilton (Ontario)</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Leonard, Jeffrey R" sort="Leonard, Jeffrey R" uniqKey="Leonard J" first="Jeffrey R" last="Leonard">Jeffrey R. Leonard</name>
<affiliation wicri:level="2"><nlm:aff id="Aff36">Department of Neurosurgery, Division of Pediatric Neurosurgery, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, MO USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Department of Neurosurgery, Division of Pediatric Neurosurgery, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Liau, Linda M" sort="Liau, Linda M" uniqKey="Liau L" first="Linda M" last="Liau">Linda M. Liau</name>
<affiliation wicri:level="2"><nlm:aff id="Aff38">Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Massimi, Luca" sort="Massimi, Luca" uniqKey="Massimi L" first="Luca" last="Massimi">Luca Massimi</name>
<affiliation wicri:level="3"><nlm:aff id="Aff39">Pediatric Neurosurgery, Catholic University Medical School, Rome, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Pediatric Neurosurgery, Catholic University Medical School, Rome</wicri:regionArea>
<placeName><settlement type="city">Rome</settlement>
<region nuts="2">Latium</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Pollack, Ian F" sort="Pollack, Ian F" uniqKey="Pollack I" first="Ian F" last="Pollack">Ian F. Pollack</name>
<affiliation wicri:level="2"><nlm:aff id="Aff40">Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
<wicri:cityArea>Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Ra, Young Shin" sort="Ra, Young Shin" uniqKey="Ra Y" first="Young Shin" last="Ra">Young Shin Ra</name>
<affiliation wicri:level="3"><nlm:aff id="Aff41">Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul, South Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rubin, Joshua B" sort="Rubin, Joshua B" uniqKey="Rubin J" first="Joshua B" last="Rubin">Joshua B. Rubin</name>
<affiliation wicri:level="2"><nlm:aff id="Aff37">Department of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, MO USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Missouri (État)</region>
</placeName>
<wicri:cityArea>Department of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Van Meir, Erwin G" sort="Van Meir, Erwin G" uniqKey="Van Meir E" first="Erwin G" last="Van Meir">Erwin G. Van Meir</name>
<affiliation wicri:level="2"><nlm:aff id="Aff42">Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
<wicri:cityArea>Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff43">Department of Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
<wicri:cityArea>Department of Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Wang, Kyu Chang" sort="Wang, Kyu Chang" uniqKey="Wang K" first="Kyu-Chang" last="Wang">Kyu-Chang Wang</name>
<affiliation wicri:level="3"><nlm:aff id="Aff22">Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul, South Korea</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea>Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul</wicri:regionArea>
<placeName><settlement type="city">Séoul</settlement>
<region type="capital">Région capitale de Séoul</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Weiss, William A" sort="Weiss, William A" uniqKey="Weiss W" first="William A" last="Weiss">William A. Weiss</name>
<affiliation wicri:level="2"><nlm:aff id="Aff44">Department of Neurological Surgery, University of California San Francisco, San Francisco, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Neurological Surgery, University of California San Francisco, San Francisco</wicri:cityArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff45">Department of Paediatrics, University of California San Francisco, San Francisco, CA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Californie</region>
</placeName>
<wicri:cityArea>Department of Paediatrics, University of California San Francisco, San Francisco</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Zitterbart, Karel" sort="Zitterbart, Karel" uniqKey="Zitterbart K" first="Karel" last="Zitterbart">Karel Zitterbart</name>
<affiliation wicri:level="3"><nlm:aff id="Aff46">Department of Pediatric Oncology, University Hospital Brno and Masaryk University School of Medicine, Brno, Czech Republic and Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic</nlm:aff>
<country xml:lang="fr">République tchèque</country>
<wicri:regionArea>Department of Pediatric Oncology, University Hospital Brno and Masaryk University School of Medicine, Brno, Czech Republic and Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno</wicri:regionArea>
<placeName><settlement type="city">Brno</settlement>
<region>Moravie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bristow, Robert G" sort="Bristow, Robert G" uniqKey="Bristow R" first="Robert G" last="Bristow">Robert G. Bristow</name>
<affiliation><nlm:aff id="Aff6">Cellular Imaging Core, STTARR Innovation Facility/Radiation Medicine Program and Department of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Alman, Benjamin" sort="Alman, Benjamin" uniqKey="Alman B" first="Benjamin" last="Alman">Benjamin Alman</name>
<affiliation><nlm:aff id="Aff7">Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff8">Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="Aff9">Division of Orthopedic Surgery, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff10">Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hawkins, Cynthia E" sort="Hawkins, Cynthia E" uniqKey="Hawkins C" first="Cynthia E" last="Hawkins">Cynthia E. Hawkins</name>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff5">Division of Pathology, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Malkin, David" sort="Malkin, David" uniqKey="Malkin D" first="David" last="Malkin">David Malkin</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, 555 University Avenue, M5G 1X8 Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff8">Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="Aff47">Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Clifford, Steven C" sort="Clifford, Steven C" uniqKey="Clifford S" first="Steven C" last="Clifford">Steven C. Clifford</name>
<affiliation wicri:level="1"><nlm:aff id="Aff48">Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne</wicri:regionArea>
<wicri:noRegion>Newcastle-upon-Tyne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pfister, Stefan M" sort="Pfister, Stefan M" uniqKey="Pfister S" first="Stefan M" last="Pfister">Stefan M. Pfister</name>
<affiliation wicri:level="3"><nlm:aff id="Aff13">Division of Molecular Genetics, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Division of Molecular Genetics, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="Aff14">Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg</wicri:regionArea>
<placeName><region type="land" nuts="1">Bade-Wurtemberg</region>
<region type="district" nuts="2">District de Karlsruhe</region>
<settlement type="city">Heidelberg</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Taylor, Michael D" sort="Taylor, Michael D" uniqKey="Taylor M" first="Michael D" last="Taylor">Michael D. Taylor</name>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation><nlm:aff id="Aff3">Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="Aff4">Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tabori, Uri" sort="Tabori, Uri" uniqKey="Tabori U" first="Uri" last="Tabori">Uri Tabori</name>
<affiliation wicri:level="4"><nlm:aff id="Aff1">Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, 555 University Avenue, M5G 1X8 Toronto, ON Canada</nlm:aff>
<orgName type="university">Université de Toronto</orgName>
<country>Canada</country>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
<affiliation><nlm:aff id="Aff2">The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</nlm:aff>
<wicri:noCountry code="subfield">ON Canada</wicri:noCountry>
</affiliation>
</author>
</analytic>
<series><title level="j">Acta Neuropathologica Communications</title>
<idno type="eISSN">2051-5960</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p><italic>TP53</italic>
mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates <italic>TP53</italic>
related radioresistance and can be used to sensitize <italic>TP53</italic>
mutant tumors for radiation. We examined the subgroup-specific role of <italic>TP53</italic>
mutations in a cohort of 314 patients treated with radiation. <italic>TP53</italic>
wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of <italic>TP53</italic>
mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/<italic>TP53</italic>
mutant medulloblastoma had higher 5-year survival than those with SHH/<italic>TP53</italic>
mutant tumours (100% and 36.6% ± 8.7%, respectively (p < 0.001)). Introduction of <italic>TP53</italic>
mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89% ± 2% vs. 57.4% ± 1.8% (p < 0.01)). In contrast, β-catenin mutation sensitized <italic>TP53</italic>
mutant cells to radiation (p < 0.05). Lithium, an activator of the WNT pathway, sensitized <italic>TP53</italic>
mutant medulloblastoma to radiation (SF2 of 43.5% ± 1.5% in lithium treated cells vs. 56.6 ± 3% (p < 0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33% ± 8% for lithium treated cells vs. 27% ± 3% for untreated controls (p = 0.05). Poor survival of patients with <italic>TP53</italic>
mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes <italic>TP53</italic>
mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.</p>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s40478-014-0174-y) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Acta Neuropathol Commun</journal-id>
<journal-id journal-id-type="iso-abbrev">Acta Neuropathol Commun</journal-id>
<journal-title-group><journal-title>Acta Neuropathologica Communications</journal-title>
</journal-title-group>
<issn pub-type="epub">2051-5960</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25539912</article-id>
<article-id pub-id-type="pmc">4297452</article-id>
<article-id pub-id-type="publisher-id">174</article-id>
<article-id pub-id-type="doi">10.1186/s40478-014-0174-y</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>WNT activation by lithium abrogates <italic>TP53</italic>
mutation associated radiation resistance in medulloblastoma</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Zhukova</surname>
<given-names>Nataliya</given-names>
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<address><email>nataliya.zhukova@sickkids.ca</email>
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<address><email>bognarlaszlo@t-email.hu</email>
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<contrib contrib-type="author"><name><surname>Cho</surname>
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<given-names>Charles G</given-names>
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<address><email>ceberha@jhmi.edu</email>
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<contrib contrib-type="author"><name><surname>Conter</surname>
<given-names>Cecile Faure</given-names>
</name>
<address><email>cecile.conter@lyon.unicancer.fr</email>
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<xref ref-type="aff" rid="Aff24"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fouladi</surname>
<given-names>Maryam</given-names>
</name>
<address><email>maryam.fouladi@cchmc.org</email>
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</contrib>
<contrib contrib-type="author"><name><surname>French</surname>
<given-names>Pim J</given-names>
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<given-names>Wieslawa A</given-names>
</name>
<address><email>w.grajkowska@czd.pl</email>
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<address><email>guptan@neurosurg.ucsf.edu</email>
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<xref ref-type="aff" rid="Aff29"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hauser</surname>
<given-names>Peter</given-names>
</name>
<address><email>hauserpeti@yahoo.com</email>
</address>
<xref ref-type="aff" rid="Aff30"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jabado</surname>
<given-names>Nada</given-names>
</name>
<address><email>nada.jabado@mcgill.ca</email>
</address>
<xref ref-type="aff" rid="Aff31"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vasiljevic</surname>
<given-names>Alexandre</given-names>
</name>
<address><email>alexandre.vasiljevic@chu-lyon.fr</email>
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<xref ref-type="aff" rid="Aff32"></xref>
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<given-names>Shin</given-names>
</name>
<address><email>sjung@chonnam.ac.kr</email>
</address>
<xref ref-type="aff" rid="Aff33"></xref>
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<given-names>Seung-Ki</given-names>
</name>
<address><email>nsthomas@snu.ac.kr</email>
</address>
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<contrib contrib-type="author"><name><surname>Klekner</surname>
<given-names>Almos</given-names>
</name>
<address><email>aklekner@yahoo.com</email>
</address>
<xref ref-type="aff" rid="Aff21"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kumabe</surname>
<given-names>Toshihiro</given-names>
</name>
<address><email>ku.ma@nsg.med.tohoku.ac.jp</email>
</address>
<xref ref-type="aff" rid="Aff34"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lach</surname>
<given-names>Boleslaw</given-names>
</name>
<address><email>lach@hhsc.ca</email>
</address>
<xref ref-type="aff" rid="Aff35"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Leonard</surname>
<given-names>Jeffrey R</given-names>
</name>
<address><email>jeffrey.leonard@nationwidechildrens.org</email>
</address>
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<given-names>Linda M</given-names>
</name>
<address><email>LLIAU@mednet.ucla.edu</email>
</address>
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<given-names>Luca</given-names>
</name>
<address><email>lmassimi@email.it</email>
</address>
<xref ref-type="aff" rid="Aff39"></xref>
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<contrib contrib-type="author"><name><surname>Pollack</surname>
<given-names>Ian F</given-names>
</name>
<address><email>ian.pollack@chp.edu</email>
</address>
<xref ref-type="aff" rid="Aff40"></xref>
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<given-names>Young Shin</given-names>
</name>
<address><email>ysra@amc.seoul.kr</email>
</address>
<xref ref-type="aff" rid="Aff41"></xref>
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<given-names>Joshua B</given-names>
</name>
<address><email>rubin_j@kids.wustl.edu</email>
</address>
<xref ref-type="aff" rid="Aff37"></xref>
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<given-names>Erwin G</given-names>
</name>
<address><email>evanmei@emory.edu</email>
</address>
<xref ref-type="aff" rid="Aff42"></xref>
<xref ref-type="aff" rid="Aff43"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Kyu-Chang</given-names>
</name>
<address><email>kcwang@snu.ac.kr</email>
</address>
<xref ref-type="aff" rid="Aff22"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Weiss</surname>
<given-names>William A</given-names>
</name>
<address><email>waweiss@gmail.com</email>
</address>
<xref ref-type="aff" rid="Aff44"></xref>
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</contrib>
<contrib contrib-type="author"><name><surname>Zitterbart</surname>
<given-names>Karel</given-names>
</name>
<address><email>kzitterbart@fnbrno.cz</email>
</address>
<xref ref-type="aff" rid="Aff46"></xref>
</contrib>
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<given-names>Robert G</given-names>
</name>
<address><email>rob.bristow@rmp.uhn.on.ca</email>
</address>
<xref ref-type="aff" rid="Aff6"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Alman</surname>
<given-names>Benjamin</given-names>
</name>
<address><email>benjamine.alman@sickkids.ca</email>
</address>
<xref ref-type="aff" rid="Aff7"></xref>
<xref ref-type="aff" rid="Aff8"></xref>
<xref ref-type="aff" rid="Aff9"></xref>
<xref ref-type="aff" rid="Aff10"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hawkins</surname>
<given-names>Cynthia E</given-names>
</name>
<address><email>cynthia.hawkins@sickkids.ca</email>
</address>
<xref ref-type="aff" rid="Aff2"></xref>
<xref ref-type="aff" rid="Aff5"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Malkin</surname>
<given-names>David</given-names>
</name>
<address><email>david.malkin@sickkids.ca</email>
</address>
<xref ref-type="aff" rid="Aff1"></xref>
<xref ref-type="aff" rid="Aff8"></xref>
<xref ref-type="aff" rid="Aff47"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Clifford</surname>
<given-names>Steven C</given-names>
</name>
<address><email>steve.clifford@ncl.ac.uk</email>
</address>
<xref ref-type="aff" rid="Aff48"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pfister</surname>
<given-names>Stefan M</given-names>
</name>
<address><email>s.pfister@dkfz.de</email>
</address>
<xref ref-type="aff" rid="Aff13"></xref>
<xref ref-type="aff" rid="Aff14"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Taylor</surname>
<given-names>Michael D</given-names>
</name>
<address><email>mdtaylor@sickkids.ca</email>
</address>
<xref ref-type="aff" rid="Aff2"></xref>
<xref ref-type="aff" rid="Aff3"></xref>
<xref ref-type="aff" rid="Aff4"></xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Tabori</surname>
<given-names>Uri</given-names>
</name>
<address><email>uri.tabori@sickkids.ca</email>
</address>
<xref ref-type="aff" rid="Aff1"></xref>
<xref ref-type="aff" rid="Aff2"></xref>
</contrib>
<aff id="Aff1"><label></label>
Division of Hematology/Oncology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, 555 University Avenue, M5G 1X8 Toronto, ON Canada</aff>
<aff id="Aff2"><label></label>
The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON Canada</aff>
<aff id="Aff3"><label></label>
Division of Neurosurgery, The Hospital for Sick Children, Toronto, ON Canada</aff>
<aff id="Aff4"><label></label>
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON Canada</aff>
<aff id="Aff5"><label></label>
Division of Pathology, The Hospital for Sick Children, Toronto, ON Canada</aff>
<aff id="Aff6"><label></label>
Cellular Imaging Core, STTARR Innovation Facility/Radiation Medicine Program and Department of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, ON Canada</aff>
<aff id="Aff7"><label></label>
Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON Canada</aff>
<aff id="Aff8"><label></label>
Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON Canada</aff>
<aff id="Aff9"><label></label>
Division of Orthopedic Surgery, The Hospital for Sick Children, Toronto, ON Canada</aff>
<aff id="Aff10"><label></label>
Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON Canada</aff>
<aff id="Aff11"><label></label>
Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON Canada</aff>
<aff id="Aff12"><label></label>
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology University Medical Center, Gottingen, Germany</aff>
<aff id="Aff13"><label></label>
Division of Molecular Genetics, University Hospital, Heidelberg, Germany</aff>
<aff id="Aff14"><label></label>
Department of Paediatric Oncology, Haematology and Immunology, University Hospital, Heidelberg, Germany</aff>
<aff id="Aff15"><label></label>
CCU Neuropathology, DKFZ and Department of Neuropathology, University Hospital, Heidelberg, Germany</aff>
<aff id="Aff16"><label></label>
Princess Margaret Cancer Centre, University Health Network, Toronto, ON Canada</aff>
<aff id="Aff17"><label></label>
Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA USA</aff>
<aff id="Aff18"><label></label>
Department of Neurology, Stanford University, San Francisco, CA USA</aff>
<aff id="Aff19"><label></label>
Institute of Neuropathology, University of Bonn Medical Centre, Bonn, Germany</aff>
<aff id="Aff20"><label></label>
Department of Paediatric Haematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany</aff>
<aff id="Aff21"><label></label>
Department of Neurosurgery, University of Debrecen, Clinical Centre, Debrecen, Hungary</aff>
<aff id="Aff22"><label></label>
Division of Pediatric Neurosurgery, Seoul National University Children’s Hospital, Seoul, South Korea</aff>
<aff id="Aff23"><label></label>
Departments of Pathology, Ophthalmology and Oncology, John Hopkins University School of Medicine, Baltimore, MD USA</aff>
<aff id="Aff24"><label></label>
Department of Paediatrics, Institute of Hematology and Pediatric Oncology, Lyon, France</aff>
<aff id="Aff25"><label></label>
Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH USA</aff>
<aff id="Aff26"><label></label>
Department of Pathology and Neurology, Erasmus Medical Center, Rotterdam, Netherlands</aff>
<aff id="Aff27"><label></label>
Department of Pathology, The Children’s Memorial Health Institute, Warsaw, Poland</aff>
<aff id="Aff28"><label></label>
Departments of Neurological Surgery, University of California San Francisco, San Francisco, CA USA</aff>
<aff id="Aff29"><label></label>
Department of Pediatrics, University of California San Francisco, San Francisco, CA USA</aff>
<aff id="Aff30"><label></label>
Department of Pediatrics, Semmelweis University, Budapest, Hungary</aff>
<aff id="Aff31"><label></label>
Department of Pediatrics, Division of Haemato-Oncology, McGill University, Montreal, QC Canada</aff>
<aff id="Aff32"><label></label>
Centre de Pathologie EST, Groupement Hospitalier EST, Hospices Civils de Lyon, Bron, France</aff>
<aff id="Aff33"><label></label>
Department of Neurosurgery, Université Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hospital and Medical School, Hwasun-gun, Chonnam South Korea</aff>
<aff id="Aff34"><label></label>
Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan</aff>
<aff id="Aff35"><label></label>
Department of Pathology and Molecular Medicine, Division of Anatomical Pathology, McMaster University, Hamilton, ON Canada</aff>
<aff id="Aff36"><label></label>
Department of Neurosurgery, Division of Pediatric Neurosurgery, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, MO USA</aff>
<aff id="Aff37"><label></label>
Department of Pediatrics, Anatomy and Neurobiology, Washington University School of Medicine and St. Louis Children’s Hospital, St. Louis, MO USA</aff>
<aff id="Aff38"><label></label>
Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA USA</aff>
<aff id="Aff39"><label></label>
Pediatric Neurosurgery, Catholic University Medical School, Rome, Italy</aff>
<aff id="Aff40"><label></label>
Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA USA</aff>
<aff id="Aff41"><label></label>
Department of Neurosurgery, University of Ulsan, Asan Medical Center, Seoul, South Korea</aff>
<aff id="Aff42"><label></label>
Department of Neurosurgery, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA USA</aff>
<aff id="Aff43"><label></label>
Department of Hematology & Medical Oncology, School of Medicine and Winship Cancer Institute, Emory University, Atlanta, GA USA</aff>
<aff id="Aff44"><label></label>
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA USA</aff>
<aff id="Aff45"><label></label>
Department of Paediatrics, University of California San Francisco, San Francisco, CA USA</aff>
<aff id="Aff46"><label></label>
Department of Pediatric Oncology, University Hospital Brno and Masaryk University School of Medicine, Brno, Czech Republic and Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic</aff>
<aff id="Aff47"><label></label>
Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON Canada</aff>
<aff id="Aff48"><label></label>
Northern Institute for Cancer Research, Newcastle University, Newcastle-upon-Tyne, United Kingdom</aff>
<aff id="Aff49"><label></label>
Departamento de Ciências Biomédicas e Medicina, Regenerative Medicine Program, Universidade do Algarve, 8005-139 Faro, Portugal</aff>
<aff id="Aff50"><label></label>
Centre for Molecular and Structural Biomedicine, CBME/IBB, LA. University of Algarve, 8005-139 Faro, Portugal</aff>
<aff id="Aff51"><label></label>
Department of Medical Biophysics, University of Toronto, Toronto, ON Canada</aff>
<aff id="Aff52"><label></label>
Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden</aff>
<aff id="Aff53"><label></label>
Department of Clinical Genetics, Uppsala University Hospital, Uppsala, Sweden</aff>
</contrib-group>
<pub-date pub-type="epub"><day>24</day>
<month>12</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>24</day>
<month>12</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="collection"><year>2014</year>
</pub-date>
<volume>2</volume>
<elocation-id>174</elocation-id>
<history><date date-type="received"><day>27</day>
<month>11</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>2</day>
<month>12</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>© Zhukova et al.; licensee BioMed Central. 2014</copyright-statement>
<license license-type="open-access"><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0">http://creativecommons.org/licenses/by/4.0</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<abstract id="Abs1"><p><italic>TP53</italic>
mutations confer subgroup specific poor survival for children with medulloblastoma. We hypothesized that WNT activation which is associated with improved survival for such children abrogates <italic>TP53</italic>
related radioresistance and can be used to sensitize <italic>TP53</italic>
mutant tumors for radiation. We examined the subgroup-specific role of <italic>TP53</italic>
mutations in a cohort of 314 patients treated with radiation. <italic>TP53</italic>
wild-type or mutant human medulloblastoma cell-lines and normal neural stem cells were used to test radioresistance of <italic>TP53</italic>
mutations and the radiosensitizing effect of WNT activation on tumors and the developing brain. Children with WNT/<italic>TP53</italic>
mutant medulloblastoma had higher 5-year survival than those with SHH/<italic>TP53</italic>
mutant tumours (100% and 36.6% ± 8.7%, respectively (p < 0.001)). Introduction of <italic>TP53</italic>
mutation into medulloblastoma cells induced radioresistance (survival fractions at 2Gy (SF2) of 89% ± 2% vs. 57.4% ± 1.8% (p < 0.01)). In contrast, β-catenin mutation sensitized <italic>TP53</italic>
mutant cells to radiation (p < 0.05). Lithium, an activator of the WNT pathway, sensitized <italic>TP53</italic>
mutant medulloblastoma to radiation (SF2 of 43.5% ± 1.5% in lithium treated cells vs. 56.6 ± 3% (p < 0.01)) accompanied by increased number of γH2AX foci. Normal neural stem cells were protected from lithium induced radiation damage (SF2 of 33% ± 8% for lithium treated cells vs. 27% ± 3% for untreated controls (p = 0.05). Poor survival of patients with <italic>TP53</italic>
mutant medulloblastoma may be related to radiation resistance. Since constitutive activation of the WNT pathway by lithium sensitizes <italic>TP53</italic>
mutant medulloblastoma cells and protect normal neural stem cells from radiation, this oral drug may represent an attractive novel therapy for high-risk medulloblastomas.</p>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s40478-014-0174-y) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2014</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Allemagne</li>
<li>Canada</li>
<li>Corée du Sud</li>
<li>France</li>
<li>Hongrie</li>
<li>Italie</li>
<li>Japon</li>
<li>Pays-Bas</li>
<li>Pologne</li>
<li>Portugal</li>
<li>Royaume-Uni</li>
<li>République tchèque</li>
<li>Suède</li>
<li>États-Unis</li>
</country>
<region><li>Auvergne-Rhône-Alpes</li>
<li>Bade-Wurtemberg</li>
<li>Californie</li>
<li>District de Cologne</li>
<li>District de Karlsruhe</li>
<li>East Middle Sweden</li>
<li>Géorgie (États-Unis)</li>
<li>Hambourg</li>
<li>Hollande-Méridionale</li>
<li>Hongrie centrale</li>
<li>Latium</li>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Missouri (État)</li>
<li>Moravie</li>
<li>Ohio</li>
<li>Ontario</li>
<li>Pennsylvanie</li>
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<li>Rhénanie-du-Nord-Westphalie</li>
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<li>Région capitale de Séoul</li>
<li>Svealand</li>
</region>
<settlement><li>Bonn</li>
<li>Brno</li>
<li>Budapest</li>
<li>Hambourg</li>
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<li>Heidelberg</li>
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<li>Montréal</li>
<li>Rome</li>
<li>Rotterdam</li>
<li>Séoul</li>
<li>Toronto</li>
<li>Uppsala</li>
</settlement>
<orgName><li>Université McGill</li>
<li>Université McMaster</li>
<li>Université d'Uppsala</li>
<li>Université de Toronto</li>
</orgName>
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