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.

Clinical Cooperation Unit Neuropathology German Cancer Research Center Heidelberg Germany

Clinical Cooperation Unit Pediatric Oncology German Cancer Research Center Heidelberg Germany

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

Department of Neuropathology Institute of Pathology Heidelberg University Hospital Heidelberg Germany

Department of Neuropathology NN Burdenko Neurosurgical Institute Moscow Russia

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

Department of Pathology Motol University Hospital Charles University Prague Czech Republic

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

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

Department of Pediatric Oncology and Hematology Essen University Hospital Essen Germany

Department of Pediatric Oncology Hematology and Immunology Heidelberg University Hospital Heidelberg Germany

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

Division of Pediatric Glioma Research German Cancer Research Center Heidelberg Germany

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

Division of Pediatric Neurooncology German Cancer Research Center Heidelberg Germany

Hopp Children's Cancer Center Heidelberg Heidelberg Germany

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

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Clinical and molecular study of radiation-induced gliomas