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

Adolescent Biomarkers, Tumor / genetics Brain Neoplasms / classification Child Child, Preschool Cohort Studies DNA Copy Number Variations Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Rearrangement Glioma / classification Humans Infant Infant, Newborn Male Mitogen-Activated Protein Kinases / genetics Mutation Neurofibromin 1 / genetics Oncogene Proteins, Fusion / genetics Proto-Oncogene Proteins B-raf / genetics ras Proteins / genetics
RAS/MAPK pathway brain tumor low-grade glioma molecular diagnostics neurooncology pediatric risk stratification

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
13 04 2020
Historique:
received: 03 01 2020
revised: 27 01 2020
accepted: 12 03 2020
entrez: 15 4 2020
pubmed: 15 4 2020
medline: 3 11 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.ccell.2020.03.011 PMID: 32289278 PMC: PMC7169997
pubmed: 32289278
pii: S1535-6108(20)30151-3
doi: 10.1016/j.ccell.2020.03.011
pmc: PMC7169997
mid: NIHMS1578695
pii:
doi:

Substances chimiques

BRAF-KIAA1549 fusion protein, human 0
Biomarkers, Tumor 0
NF1 protein, human 0
Neurofibromin 1 0
Oncogene Proteins, Fusion 0
BRAF protein, human EC 2.7.11.1
Proto-Oncogene Proteins B-raf EC 2.7.11.1
Mitogen-Activated Protein Kinases EC 2.7.11.24
ras Proteins EC 3.6.5.2

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

569-583.e5

Subventions

Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : CIHR
ID : 159805
Pays : Canada

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Interests The authors declare no competing interests.

Auteurs

Scott Ryall (S)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Michal Zapotocky (M)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.

Kohei Fukuoka (K)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.

Liana Nobre (L)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.

Ana Guerreiro Stucklin (A)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.

Julie Bennett (J)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.

Robert Siddaway (R)

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

Christopher Li (C)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Sanja Pajovic (S)

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

Anthony Arnoldo (A)

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

Paul E Kowalski (PE)

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

Monique Johnson (M)

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

Javal Sheth (J)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.

Alvaro Lassaletta (A)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Pediatric Hematology and Oncology, Hospital Universitario Niño Jesús, Madrid, Spain.

Ruth G Tatevossian (RG)

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

Wilda Orisme (W)

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

Ibrahim Qaddoumi (I)

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

Lea F Surrey (LF)

Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Marilyn M Li (MM)

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

Angela J Waanders (AJ)

Department of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Hematology, Oncology, and Stem Cell Transplant, Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, IL, USA; Department of Pediatrics, Feinberg School of Medicine Northwestern University, Chicago, IL, USA.

Stephen Gilheeney (S)

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

Marc Rosenblum (M)

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

Tejus Bale (T)

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

Derek S Tsang (DS)

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Normand Laperriere (N)

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Abhaya Kulkarni (A)

Department of Surgery, University of Toronto, Toronto, ON, Canada; Department of Neurosurgery, The Hospital for Sick Children, Toronto ON, Canada.

George M Ibrahim (GM)

Department of Surgery, University of Toronto, Toronto, ON, Canada; Department of Neurosurgery, The Hospital for Sick Children, Toronto ON, Canada.

James Drake (J)

Department of Surgery, University of Toronto, Toronto, ON, Canada; Department of Neurosurgery, The Hospital for Sick Children, Toronto ON, Canada.

Peter Dirks (P)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Neurosurgery, The Hospital for Sick Children, Toronto ON, Canada.

Michael D Taylor (MD)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Neurosurgery, The Hospital for Sick Children, Toronto ON, Canada.

James T Rutka (JT)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Neurosurgery, The Hospital for Sick Children, Toronto ON, Canada.

Suzanne Laughlin (S)

Department of Radiology, The Hospital for Sick Children, Toronto ON, Canada; Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.

Manohar Shroff (M)

Department of Radiology, The Hospital for Sick Children, Toronto ON, Canada; Department of Medical Imaging, University of Toronto, Toronto, ON, Canada.

Mary Shago (M)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.

Lili-Naz Hazrati (LN)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology, The Hospital for Sick Children, Toronto, ON, Canada.

Colleen D'Arcy (C)

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Anatomical Pathology, The Alfred Hospital, Prahran, VIC, Australia.

Vijay Ramaswamy (V)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, University of Toronto, Toronto, ON, Canada.

Ute Bartels (U)

Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, University of Toronto, Toronto, ON, Canada.

Annie Huang (A)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada.

Eric Bouffet (E)

Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Paediatrics, University of Toronto, Toronto, ON, Canada.

Matthias A Karajannis (MA)

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

Mariarita Santi (M)

Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Genomic Diagnostics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

David W Ellison (DW)

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

Uri Tabori (U)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.

Cynthia Hawkins (C)

Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology, The Hospital for Sick Children, Toronto, ON, Canada. Electronic address: cynthia.hawkins@sickkids.ca.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Enfant d'âge préscolaire › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Phénomènes génétiques › Réarrangement des gènes › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs du tissu nerveux › Tumeurs neuroectodermiques › Tumeurs neuroépitheliales › Gliome › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › Nouveau-né › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Mitogen-Activated Protein Kinases › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Neurofibromine-1 › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines de fusion oncogènes › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Kinases raf › Protéines proto-oncogènes B-raf › Integrated Molecular and Clinical Analysis of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines G › Protéines G monomériques › Protéines G ras › Integrated Molecular and Clinical Analysis of...