Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.

Autor:	Nussbaumer G; Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria., Benesch M; Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria., Grabovska Y; Division of Molecular Pathology, Institute of Cancer Research, London, UK., Mackay A; Division of Molecular Pathology, Institute of Cancer Research, London, UK., Castel D; U981, Molecular Predictors and New Targets in Oncology, Team Genomics and Oncogenesis of Pediatric Brain Tumors, INSERM, Gustave Roussy, Université Paris-Saclay, Villejuif, France.; Department of Pediatric and Adolescent Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Grill J; U981, Molecular Predictors and New Targets in Oncology, Team Genomics and Oncogenesis of Pediatric Brain Tumors, INSERM, Gustave Roussy, Université Paris-Saclay, Villejuif, France.; Department of Pediatric and Adolescent Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Alonso MM; Department of Pediatrics, Clínica Universidad de Navarra, Pamplona, Spain.; Solid Tumor Program, Center for the Applied Medical Research, Pamplona, Navarra, Spain.; Health Research Institute of Navarra (IdiSNA), Pamplona, Navarra, Spain., Antonelli M; Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University, Rome, Italy., Bailey S; Department of Paediatric Oncology, Sir James Spence Institute of Child Health, Royal Victoria Infirmary Queen Victoria Road, Newcastle upon Tyne, UK., Baugh JN; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Biassoni V; Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Blattner-Johnson M; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany., Broniscer A; Division of Hematology-Oncology, Children's Hospital of Pittsburgh, Pittsburgh, PA, U.S.A., Carai A; Neurosurgery Unit, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy., Colafati GS; Oncological Neuroradiology and Advanced Diagnostics Unit, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy., Colditz N; Division of Pediatric Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany., Corbacioglu S; Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany., Crampsie S; Division of Molecular Pathology, Institute of Cancer Research, London, UK., Entz-Werle N; UMR CNRS 7021-Laboratory of Bioimagery and Pathologies Team tumor signaling and therapeutic targets, University of Strasbourg, Illkirch, France.; Pediatric Onco-Hematology Department-Pediatrics III, University Hospital of Strasbourg, Strasbourg, France., Eyrich M; Pediatric Hematology and Oncology, Department of Pediatrics, University Hospital Würzburg, Würzburg, Germany., Friker LL; Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn Medical Center, Bonn, Germany., Frühwald MC; Pediatric and Adolescent Medicine, Swabian Children's Cancer Center, University Medical Center Augsburg, Augsburg, Germany., Garrè ML; Neuro-Oncology Unit, IRCSS Istituto Giannina Gaslini, Genoa, Italy., Gerber NU; Department of Oncology and Children's Research Centre, University Children's Hospital, Zurich, Switzerland., Giangaspero F; Department of Radiological, Oncological and Anatomo-Pathological Sciences, Sapienza University, Rome, Italy., Gil-da-Costa MJ; Pediatric Oncology Department, University Hospital São João, Porto, Portugal., Graf N; Department of Pediatric Oncology and Hematology, Saarland University, Homburg, Germany., Hargrave D; Pediatric Oncology, Great Ormond Street Hospital for Children, London, UK., Hauser P; Second Department of Pediatrics, Semmelweis University, Budapest, Hungary., Herrlinger U; Division of Clinical Neuro-Oncology, Department of Neurology, University Hospital Bonn, Bonn, Germany., Hoffmann M; Division of Pediatric Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany., Hulleman E; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Izquierdo E; Division of Molecular Pathology, Institute of Cancer Research, London, UK., Jacobs S; Department of Pediatric Hematology and Oncology, University Hospitals Leuven, Belgium.; Pediatric Oncology, Department of Oncology, KU Leuven, Belgium., Karremann M; Department of Pediatric and Adolescent Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Kattamis A; Division of Pediatric Hematology-Oncology, First Department of Pediatrics, National and Kapodistrian University of Athens, 'Aghia Sophia' Children's Hospital, Athens, Greece., Kebudi R; Division of Pediatric Hematology-Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey., Kortmann RD; Department of Radiation Oncology, University of Leipzig, Leipzig, Germany., Kwiecien R; Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany., Massimino M; Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Mastronuzzi A; Department of Onco-Hematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy., Miele E; Department of Onco-Hematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy., Morana G; Department of Neurosciences, University of Turin, Turin, Italy., Noack CM; Center of Radiology, Department of Diagnostic and Interventional Radiology and Neuroradiology, Hospital of Fulda, Fulda, Germany., Pentikainen V; Division of Hematology-Oncology and Stem Cell Transplantation, Children's Hospital, Helsinki University Hospital, Helsinki, Finland., Perwein T; Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria., Pfister SM; National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg, Germany.; Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany., Pietsch T; Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn Medical Center, Bonn, Germany., Roka K; Division of Pediatric Hematology-Oncology, First Department of Pediatrics, National and Kapodistrian University of Athens, 'Aghia Sophia' Children's Hospital, Athens, Greece., Rossi S; Pathology Unit, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy., Rutkowski S; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Schiavello E; Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy., Seidel C; Department of Radiation Oncology, University of Leipzig, Leipzig, Germany., Štěrba J; Department of Pediatric Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic., Sturm D; Department of Pediatric Oncology, Hematology & Immunology, Heidelberg University Hospital, Heidelberg, Germany.; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany., Sumerauer D; Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic., Tacke A; Division of Pediatric Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany., Temelso S; Division of Molecular Pathology, Institute of Cancer Research, London, UK., Valentini C; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany., van Vuurden D; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Varlet P; GHU-Paris Psychiatry and Neuroscience, Sainte-Anne Hospital, Department of Neuropathology, Paris, France., Veldhuijzen van Zanten SEM; Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Vinci M; Department of Onco-Hematology, Gene and Cell Therapy, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy., von Bueren AO; Department of Pediatrics, Obstetrics and Gynecology, Division of Pediatric Hematology and Oncology, University Hospital Geneva, Geneva, Switzerland., Warmuth-Metz M; Institute of Diagnostic and Interventional Neuroradiology, University of Würzburg, Würzburg, Germany., Wesseling P; Department of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.; Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., Wiese M; Neurosurgery Unit, Bambino Gesù Children's Hospital (IRCCS), Rome, Italy., Wolff JEA; AbbVie Inc, Oncology Development, North Chicago, IL, U.S.A., Zamecnik J; Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague and University Hospital Motol, Prague, Czech Republic., Morales La Madrid A; Pediatric Neuro-Oncology, Pediatric Cancer Center Barcelona, Hospital Sant Joan de Deu, Barcelona, Spain., Bison B; Neuroradiological Reference Center for the Pediatric Brain Tumor (HIT) Studies of the German Society of Pediatric Oncology and Hematology, University Augsburg, Faculty of Medicine, Germany.; Diagnostic and Interventional Neuroradiology, Faculty of Medicine, University of Augsburg, Augsburg, Germany., Gielen GH; Institute of Neuropathology, DGNN Brain Tumor Reference Center, University of Bonn Medical Center, Bonn, Germany., Jones DTW; Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.; Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany., Jones C; Division of Molecular Pathology, Institute of Cancer Research, London, UK., Kramm CM; Division of Pediatric Hematology and Oncology, University Medical Center Göttingen, Göttingen, Germany.
Jazyk:	angličtina
Zdroj:	Neuro-oncology [Neuro Oncol] 2024 Sep 05; Vol. 26 (9), pp. 1723-1737.
DOI:	10.1093/neuonc/noae080
Abstrakt:	Background: The term gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features could not be established. Methods: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization. Results: Median overall survival (OS) was 15.5 months (interquartile range, 10.9-27.7) with a 2-year survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2-55.7); grade III: 15.9 months (11.4-26.3); grade IV: 10.4 months (8.8-14.4). By DNA methylation profiling (n = 49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wild-type (n = 31/49, 63.3%) with enriched subclasses pedHGG_RTK2 (n = 19), pedHGG_A/B (n = 6), and pedHGG_MYCN (n = 5), but only one pedHGG_RTK1 case. Within the pedHGG, H3-/IDH-wild-type subgroup, recurrent alterations in EGFR (n = 10) and BCOR (n = 9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wild-type subgroup TP53 alterations had a significant negative effect on OS. Conclusions: Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG_RTK2, pedHGG_A/B, EGFR and BCOR mutations, chromosome 6 rearrangements). (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)
Databáze:	MEDLINE
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