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Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors
P. Sievers, SC. Henneken, C. Blume, M. Sill, D. Schrimpf, D. Stichel, K. Okonechnikov, DE. Reuss, J. Benzel, KK. Maaß, M. Kool, D. Sturm, T. Zheng, DR. Ghasemi, P. Kohlhof-Meinecke, O. Cruz, M. Suñol, C. Lavarino, V. Ruf, HB. Boldt, M. Pagès, C....
Jazyk angličtina Země Německo
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
G0701018
Medical Research Council - United Kingdom
G1100578
Medical Research Council - United Kingdom
MR/N004272/1
Medical Research Council - United Kingdom
Department of Health - United Kingdom
NLK
ProQuest Central
od 1997-01-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 1997-01-01 do Před 1 rokem
Psychology Database (ProQuest)
od 1997-01-01 do Před 1 rokem
- MeSH
- dítě MeSH
- ependymom genetika MeSH
- lidé MeSH
- nádorové supresorové proteiny genetika MeSH
- onkogenní fúze MeSH
- proteiny buněčného cyklu genetika MeSH
- supratentoriální nádory genetika MeSH
- transkripční faktory genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Ependymomas encompass a heterogeneous group of central nervous system (CNS) neoplasms that occur along the entire neuroaxis. In recent years, extensive (epi-)genomic profiling efforts have identified several molecular groups of ependymoma that are characterized by distinct molecular alterations and/or patterns. Based on unsupervised visualization of a large cohort of genome-wide DNA methylation data, we identified a highly distinct group of pediatric-type tumors (n = 40) forming a cluster separate from all established CNS tumor types, of which a high proportion were histopathologically diagnosed as ependymoma. RNA sequencing revealed recurrent fusions involving the pleomorphic adenoma gene-like 1 (PLAGL1) gene in 19 of 20 of the samples analyzed, with the most common fusion being EWSR1:PLAGL1 (n = 13). Five tumors showed a PLAGL1:FOXO1 fusion and one a PLAGL1:EP300 fusion. High transcript levels of PLAGL1 were noted in these tumors, with concurrent overexpression of the imprinted genes H19 and IGF2, which are regulated by PLAGL1. Histopathological review of cases with sufficient material (n = 16) demonstrated a broad morphological spectrum of tumors with predominant ependymoma-like features. Immunohistochemically, tumors were GFAP positive and OLIG2- and SOX10 negative. In 3/16 of the cases, a dot-like positivity for EMA was detected. All tumors in our series were located in the supratentorial compartment. Median age of the patients at the time of diagnosis was 6.2 years. Median progression-free survival was 35 months (for 11 patients with data available). In summary, our findings suggest the existence of a novel group of supratentorial neuroepithelial tumors that are characterized by recurrent PLAGL1 fusions and enriched for pediatric patients.
Bioinformatics and Omics Data Analytics German Cancer Research Center Heidelberg Germany
Children's Brain Tumour Research Centre University of Nottingham Nottingham UK
Department of Clinical Research University of Southern Denmark Odense Denmark
Department of Human Genetics McGill University Montreal QC H3A 1B1 Canada
Department of Neuropathology Otto Von Guericke University Magdeburg Germany
Department of Neuropathology University of Tübingen Tübingen Germany
Department of Pathology CHRU Nancy France
Department of Pathology Hospital Sant Joan de Déu Esplugues de Llobregat Barcelona Spain
Department of Pathology Klinikum Stuttgart Stuttgart Germany
Department of Pathology NYU Langone Medical Center New York NY USA
Department of Pathology Odense University Hospital Odense Denmark
Department of Pathology St Jude Children's Research Hospital Memphis TN USA
Department of Pathology University Medical Center Utrecht Utrecht The Netherlands
Department of Pediatric Oncology Hospital Sant Joan de Déu Esplugues de Llobregat Barcelona Spain
Department of Pediatrics McGill University Montreal QC H4A 3J1 Canada
Division of Pediatric Neurooncology German Cancer Consortium Heidelberg Germany
Faculty of Biosciences Heidelberg University 69117 Heidelberg Germany
German Cancer Consortium Heidelberg Germany
German Cancer Consortium Partner Site Essen Düsseldorf Essen Düsseldorf Germany
German Cancer Consortium Partner site Frankfurt Mainz Frankfurt am Main Germany
German Cancer Research Center Heidelberg Germany
Hopp Children's Cancer Center Heidelberg Heidelberg Germany
Institute for Neuropathology University Medical Centre Göttingen Göttingen Germany
Institute of Neuropathology Heinrich Heine University Düsseldorf Germany
Institute of Neuropathology Ludwig Maximilian University Munich Germany
Institute of Neuropathology University Medical Center Hamburg Eppendorf Hamburg Germany
Institute of Neuropathology University of Giessen Giessen Germany
Laboratory of Molecular Oncology Hospital Sant Joan de Déu Esplugues de Llobregat Barcelona Spain
Manchester Royal Infirmary Manchester University NHS Foundation Trust Manchester UK
Neuro Oncology Branch National Cancer Institute Bethesda MD USA
Pediatric Glioma Research Group German Cancer Research Center Heidelberg Germany
Princess Máxima Center for Pediatric Oncology Utrecht The Netherlands
Research Institute Children's Cancer Center Hamburg Hamburg Germany
Shaukat Khanum Memorial Cancer Hospital and Research Centre Lahore Pakistan
The Research Institute of the McGill University Health Center Montreal QC H4A 3J1 Canada
Citace poskytuje Crossref.org
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- $a Recurrent fusions in PLAGL1 define a distinct subset of pediatric-type supratentorial neuroepithelial tumors / $c P. Sievers, SC. Henneken, C. Blume, M. Sill, D. Schrimpf, D. Stichel, K. Okonechnikov, DE. Reuss, J. Benzel, KK. Maaß, M. Kool, D. Sturm, T. Zheng, DR. Ghasemi, P. Kohlhof-Meinecke, O. Cruz, M. Suñol, C. Lavarino, V. Ruf, HB. Boldt, M. Pagès, C. Pouget, L. Schweizer, MEG. Kranendonk, N. Akhtar, S. Bunkowski, C. Stadelmann, U. Schüller, WC. Mueller, H. Dohmen, T. Acker, PN. Harter, C. Mawrin, R. Beschorner, S. Brandner, M. Snuderl, Z. Abdullaev, K. Aldape, MR. Gilbert, TS. Armstrong, DW. Ellison, D. Capper, K. Ichimura, G. Reifenberger, RG. Grundy, N. Jabado, L. Krskova, M. Zapotocky, A. Vicha, P. Varlet, P. Wesseling, S. Rutkowski, A. Korshunov, W. Wick, SM. Pfister, DTW. Jones, A. von Deimling, KW. Pajtler, F. Sahm
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