Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
20 09 2021
Historique:
received: 22 05 2020
accepted: 12 08 2021
entrez: 21 9 2021
pubmed: 22 9 2021
medline: 13 10 2021
Statut: epublish

Résumé

Long-term complications such as radiation-induced second malignancies occur in a subset of patients following radiation-therapy, particularly relevant in pediatric patients due to the long follow-up period in case of survival. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies such as acute lymphoblastic leukemia (ALL) and medulloblastoma (MB). We perform comprehensive (epi-) genetic and expression profiling of RIGs arising after cranial irradiation for MB (n = 23) and ALL (n = 9). Our study reveals a unifying molecular signature for the majority of RIGs, with recurrent PDGFRA amplification and loss of CDKN2A/B and an absence of somatic hotspot mutations in genes encoding histone 3 variants or IDH1/2, uncovering diagnostic markers and potentially actionable targets.

Identifiants

pubmed: 34545083
doi: 10.1038/s41467-021-25708-y
pii: 10.1038/s41467-021-25708-y
pmc: PMC8452680
doi:

Substances chimiques

CDKN2A protein, human 0
CDKN2B protein, human 0
Cyclin-Dependent Kinase Inhibitor p15 0
Cyclin-Dependent Kinase Inhibitor p16 0
Receptor, Platelet-Derived Growth Factor alpha EC 2.7.10.1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5530

Informations de copyright

© 2021. The Author(s).

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Auteurs

Maximilian Y Deng (MY)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Dominik Sturm (D)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Elke Pfaff (E)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Martin Sill (M)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Damian Stichel (D)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Gnana Prakash Balasubramanian (GP)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Stephan Tippelt (S)

Department of Pediatric Oncology and Hematology, Essen University Hospital, Essen, Germany.

Christof Kramm (C)

Division of Pediatric Hematology and Oncology, University Medical Center Goettingen, Goettingen, Germany.

Andrew M Donson (AM)

Morgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.

Adam L Green (AL)

Morgan Adams Foundation Pediatric Brain Tumor Research Program, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.

Chris Jones (C)

Division of Molecular Pathology and Division of Cancer Therapeutics, The Institute of Cancer Research, London, United Kingdom.

Jens Schittenhelm (J)

Department of Neuropathology, Institute of Pathology and Neuropathology and Comprehensive Cancer Center Tübingen-Stuttgart, Tübingen University Hospital, Tübingen, Germany.

Martin Ebinger (M)

Department of Pediatric Hematology/Oncology, Children's University Hospital, Tübingen, Germany.

Martin U Schuhmann (MU)

Department of Neurosurgery, Division of Pediatric Neurosurgery, Tübingen University Hospital, Tübingen, Germany.

Barbara C Jones (BC)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.

Cornelis M van Tilburg (CM)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Andrea Wittmann (A)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Andrey Golanov (A)

Department of Neuropathology, NN Burdenko Neurosurgical Institute, Moscow, Russia.

Marina Ryzhova (M)

Department of Neuropathology, NN Burdenko Neurosurgical Institute, Moscow, Russia.

Jonas Ecker (J)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Till Milde (T)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Olaf Witt (O)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Pediatric Oncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Felix Sahm (F)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

David Reuss (D)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

David Sumerauer (D)

Department of Pediatric Hematology and Oncology, Motol University Hospital, Charles University, Prague, Czech Republic.

Josef Zamecnik (J)

Department of Pathology, Motol University Hospital, Charles University, Prague, Czech Republic.

Andrey Korshunov (A)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Andreas von Deimling (A)

Department of Neuropathology, Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.
Clinical Cooperation Unit Neuropathology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

Stefan M Pfister (SM)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany.
Department of Pediatric Oncology, Hematology and Immunology, Heidelberg University Hospital, Heidelberg, Germany.
Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK), Heidelberg, Germany.

David T W Jones (DTW)

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Resarch Center (DKFZ), Heidelberg, Germany. david.jones@kitz-heidelberg.de.
Division of Pediatric Glioma Research, German Cancer Research Center (DKFZ), Heidelberg, Germany. david.jones@kitz-heidelberg.de.

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