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Integrated Molecular and Clinical Analysis of 1,000 Pediatric Low-Grade Gliomas

S. Ryall, M. Zapotocky, K. Fukuoka, L. Nobre, A. Guerreiro Stucklin, J. Bennett, R. Siddaway, C. Li, S. Pajovic, A. Arnoldo, PE. Kowalski, M. Johnson, J. Sheth, A. Lassaletta, RG. Tatevossian, W. Orisme, I. Qaddoumi, LF. Surrey, MM. Li, AJ....

. 2020 ; 37 (4) : 569-583.e5. [pub] 20200413

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20028267

Grantová podpora
P30 CA008748 NCI NIH HHS - United States
159805 CIHR - Canada

Pediatric low-grade gliomas (pLGG) are frequently driven by genetic alterations in the RAS-mitogen-activated protein kinase (RAS/MAPK) pathway yet show unexplained variability in their clinical outcome. To address this, we characterized a cohort of >1,000 clinically annotated pLGG. Eighty-four percent of cases harbored a driver alteration, while those without an identified alteration also often exhibited upregulation of the RAS/MAPK pathway. pLGG could be broadly classified based on their alteration type. Rearrangement-driven tumors were diagnosed at a younger age, enriched for WHO grade I histology, infrequently progressed, and rarely resulted in death as compared with SNV-driven tumors. Further sub-classification of clinical-molecular correlates stratified pLGG into risk categories. These data highlight the biological and clinical differences between pLGG subtypes and opens avenues for future treatment refinement.

2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Arthur and Sonia Labatt Brain Tumour Research Centre The Hospital for Sick Children 555 University Avenue Toronto ON M5G 1X8 Canada

Center for Data Driven Discovery in Biomedicine Children's Hospital of Philadelphia Philadelphia PA USA

Children's Research Center University Children's Hospital Zurich Zurich Switzerland

Department of Anatomical Pathology The Alfred Hospital Prahran VIC Australia

Department of Genomic Diagnostics Children's Hospital of Philadelphia Philadelphia PA USA

Department of Haematology Oncology The Hospital for Sick Children Toronto ON Canada

Department of Hematology Oncology and Stem Cell Transplant Ann and Robert H Lurie Children's Hospital of Chicago Chicago IL USA

Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada

Department of Medical Biophysics University of Toronto Toronto ON Canada

Department of Medical Imaging University of Toronto Toronto ON Canada

Department of Neurosurgery The Hospital for Sick Children Toronto ON Canada

Department of Oncology St Jude Children's Research Hospital Memphis TN USA

Department of Paediatric Laboratory Medicine The Hospital for Sick Children Toronto ON Canada

Department of Paediatrics University of Toronto Toronto ON Canada

Department of Pathology and Laboratory Medicine Children's Hospital of Philadelphia Philadelphia PA USA

Department of Pathology Memorial Sloan Kettering Cancer Center New York NY USA

Department of Pathology St Jude Children's Research Hospital Memphis TN USA

Department of Pathology The Hospital for Sick Children Toronto ON Canada

Department of Pediatric Hematology and Oncology Hospital Universitario Niño Jesús Madrid Spain

Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago IL USA

Department of Pediatrics Memorial Sloan Kettering Cancer Center New York NY USA

Department of Radiation Oncology Faculty of Medicine University of Toronto Toronto ON Canada

Department of Radiology The Hospital for Sick Children Toronto ON Canada

Department of Surgery University of Toronto Toronto ON Canada

Radiation Medicine Program Princess Margaret Cancer Centre University Health Network Toronto ON Canada

Citace poskytuje Crossref.org

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