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Amplification of th...
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Keck, Michaela KristinaGerman Cancer Research Centre,Hopp Children’s Cancer Center Heidelberg (KiTZ)
(författare)
Amplification of the PLAG-family genes—PLAGL1 and PLAGL2—is a key feature of the novel tumor type CNS embryonal tumor with PLAGL amplification
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
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2022-11-27
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Springer Science and Business Media LLC,2023
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21 s.
Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:18126edf-6718-4009-b45d-cb3fc5e380f4
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https://lup.lub.lu.se/record/18126edf-6718-4009-b45d-cb3fc5e380f4URI
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https://doi.org/10.1007/s00401-022-02516-2DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:151297922URI
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
Anmärkningar
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Pediatric central nervous system (CNS) tumors represent the most common cause of cancer-related death in children aged 0–14 years. They differ from their adult counterparts, showing extensive clinical and molecular heterogeneity as well as a challenging histopathological spectrum that often impairs accurate diagnosis. Here, we use DNA methylation-based CNS tumor classification in combination with copy number, RNA-seq, and ChIP-seq analysis to characterize a newly identified CNS tumor type. In addition, we report histology, patient characteristics, and survival data in this tumor type. We describe a biologically distinct pediatric CNS tumor type (n = 31 cases) that is characterized by focal high-level amplification and resultant overexpression of either PLAGL1 or PLAGL2, and an absence of recurrent genetic alterations characteristic of other pediatric CNS tumor types. Both genes act as transcription factors for a regulatory subset of imprinted genes (IGs), components of the Wnt/β-Catenin pathway, and the potential drug targets RET and CYP2W1, which are also specifically overexpressed in this tumor type. A derived PLAGL-specific gene expression signature indicates dysregulation of imprinting control and differentiation/development. These tumors occurred throughout the neuroaxis including the cerebral hemispheres, cerebellum, and brainstem, and were predominantly composed of primitive embryonal-like cells lacking robust expression of markers of glial or neuronal differentiation (e.g., GFAP, OLIG2, and synaptophysin). Tumors with PLAGL1 amplification were typically diagnosed during adolescence (median age 10.5 years), whereas those with PLAGL2 amplification were diagnosed during early childhood (median age 2 years). The 10-year overall survival was 66% for PLAGL1-amplified tumors, 25% for PLAGL2-amplified tumors, 18% for male patients, and 82% for female patients. In summary, we describe a new type of biologically distinct CNS tumor characterized by PLAGL1/2 amplification that occurs predominantly in infants and toddlers (PLAGL2) or adolescents (PLAGL1) which we consider best classified as a CNS embryonal tumor and which is associated with intermediate survival. The cell of origin and optimal treatment strategies remain to be defined.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Sill, MartinGerman Cancer Research Centre,Hopp Children’s Cancer Center Heidelberg (KiTZ)
(författare)
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Wittmann, AndreaHopp Children’s Cancer Center Heidelberg (KiTZ),German Cancer Research Centre
(författare)
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Joshi, PiyushHopp Children’s Cancer Center Heidelberg (KiTZ)
(författare)
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Stichel, DamianUniversity Hospital Heidelberg,German Cancer Research Centre
(författare)
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Beck, PengboHopp Children’s Cancer Center Heidelberg (KiTZ),Heidelberg University,German Cancer Research Centre
(författare)
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Okonechnikow, KonstantinHopp Children’s Cancer Center Heidelberg (KiTZ),German Cancer Research Centre
(författare)
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Sievers, PhilippUniversity Hospital Heidelberg,German Cancer Research Centre
(författare)
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Wefers, Annika K.University Medical Center Hamburg-Eppendorf
(författare)
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Roncaroli, FedericoUniversity of Manchester
(författare)
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Avula, ShivaramAlder Hey Children’s NHS Foundation Trust
(författare)
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McCabe, Martin G.University of Manchester
(författare)
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Hayden, James T.Alder Hey Children’s NHS Foundation Trust
(författare)
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Wesseling, PieterPrincess Maxima Center for Pediatric Oncology/Hematology,Academic Medical Center of University of Amsterdam (AMC)
(författare)
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Øra, IngridLund University,Lunds universitet,Childhood Cancer Research Unit,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Skåne University Hospital(Swepub:lu)molm-ior
(författare)
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Nistér, MonicaKarolinska Institutet,Karolinska Institute
(författare)
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Kranendonk, Mariëtte E.G.Princess Maxima Center for Pediatric Oncology/Hematology
(författare)
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Tops, Bastiaan B.J.Princess Maxima Center for Pediatric Oncology/Hematology
(författare)
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Zapotocky, MichalUniversity Hospital Motol
(författare)
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Zamecnik, JosefUniversity Hospital Motol
(författare)
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Vasiljevic, AlexandreLyon Civil Hospital / Hospices Civils de Lyon
(författare)
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Fenouil, TanguyLyon Civil Hospital / Hospices Civils de Lyon
(författare)
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Meyronet, DavidLyon Civil Hospital / Hospices Civils de Lyon
(författare)
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von Hoff, KatjaBerlin Institute of Health (BIH)
(författare)
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Schüller, UlrichUniversity Medical Center Hamburg-Eppendorf,Research Institute Children’s Cancer Center Hamburg
(författare)
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Loiseau, HuguesUniversity of Bordeaux
(författare)
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Figarella-Branger, DominiqueAix-Marseille University
(författare)
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Kramm, Christof M.University Medical Center Göttingen
(författare)
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Sturm, DominikUniversity Hospital Heidelberg,Hopp Children’s Cancer Center Heidelberg (KiTZ),German Cancer Research Centre
(författare)
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Scheie, DavidCopenhagen University Hospital
(författare)
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Rauramaa, TuomasKuopio University Hospital
(författare)
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Pesola, JouniKuopio University Hospital
(författare)
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Gojo, JohannesMedical University of Vienna
(författare)
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Haberler, ChristineMedical University of Vienna
(författare)
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Brandner, SebastianUniversity College London,National Hospital for Neurology and Neurosurgery
(författare)
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Jacques, TomUCL Institute of Child Health
(författare)
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Sexton Oates, AlexandraUniversity of Melbourne
(författare)
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Saffery, RichardUniversity of Melbourne
(författare)
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Koscielniak, EwaKlinikum Stuttgart Olgahospital
(författare)
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Baker, Suzanne J.St Jude Children´s Research Hospital, Memphis
(författare)
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Yip, StephenUniversity of British Columbia
(författare)
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Snuderl, MatijaNYU Grossman School of Medicine
(författare)
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Ud Din, NasirAga Khan University, Pakistan
(författare)
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Samuel, DavidValley Children’s Hospital
(författare)
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Schramm, KathrinGerman Cancer Research Centre,Hopp Children’s Cancer Center Heidelberg (KiTZ)
(författare)
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Blattner-Johnson, MirjamHopp Children’s Cancer Center Heidelberg (KiTZ),German Cancer Research Centre
(författare)
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Selt, FlorianGerman Cancer Research Centre,Hopp Children’s Cancer Center Heidelberg (KiTZ),University Hospital Heidelberg
(författare)
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Ecker, JonasHopp Children’s Cancer Center Heidelberg (KiTZ),University Hospital Heidelberg,German Cancer Research Centre
(författare)
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Milde, TillGerman Cancer Research Centre,University Hospital Heidelberg,Hopp Children’s Cancer Center Heidelberg (KiTZ)
(författare)
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von Deimling, AndreasUniversity Hospital Heidelberg,German Cancer Research Centre
(författare)
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Korshunov, AndreyUniversity Hospital Heidelberg,German Cancer Research Centre,Hopp Children’s Cancer Center Heidelberg (KiTZ)
(författare)
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Perry, ArieUniversity of California, San Francisco
(författare)
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Pfister, Stefan MGerman Cancer Research Centre,Hopp Children’s Cancer Center Heidelberg (KiTZ),University Hospital Heidelberg
(författare)
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Sahm, FelixHopp Children’s Cancer Center Heidelberg (KiTZ),German Cancer Research Centre,University Hospital Heidelberg
(författare)
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Solomon, David A.University of California, San Francisco
(författare)
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Jones, David T WHopp Children’s Cancer Center Heidelberg (KiTZ),German Cancer Research Centre
(författare)
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German Cancer Research CentreHopp Children’s Cancer Center Heidelberg (KiTZ)
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Acta Neuropathologica: Springer Science and Business Media LLC145:1, s. 49-690001-63221432-0533
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Keck, Michaela K ...
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Sill, Martin
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Wittmann, Andrea
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Joshi, Piyush
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Stichel, Damian
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Beck, Pengbo
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visa fler...
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Okonechnikow, Ko ...
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Sievers, Philipp
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Wefers, Annika K ...
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Roncaroli, Feder ...
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Avula, Shivaram
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McCabe, Martin G ...
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Hayden, James T.
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Wesseling, Piete ...
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Øra, Ingrid
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Nistér, Monica
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Kranendonk, Mari ...
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Tops, Bastiaan B ...
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Zapotocky, Micha ...
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Zamecnik, Josef
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Vasiljevic, Alex ...
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Fenouil, Tanguy
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Meyronet, David
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von Hoff, Katja
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Schüller, Ulrich
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Loiseau, Hugues
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Figarella-Brange ...
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Kramm, Christof ...
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Sturm, Dominik
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Scheie, David
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Rauramaa, Tuomas
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Pesola, Jouni
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Gojo, Johannes
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Haberler, Christ ...
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Brandner, Sebast ...
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Sexton Oates, Al ...
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Saffery, Richard
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Koscielniak, Ewa
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Yip, Stephen
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Snuderl, Matija
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Ud Din, Nasir
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Samuel, David
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Schramm, Kathrin
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Blattner-Johnson ...
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Selt, Florian
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Ecker, Jonas
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Milde, Till
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von Deimling, An ...
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Korshunov, Andre ...
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Perry, Arie
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Pfister, Stefan ...
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Sahm, Felix
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Jones, David T W
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