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

Maximilian Y. Deng, Dominik Sturm, Elke Pfaff, Martin Sill, Damian Stichel, Gnana Prakash Balasubramanian, Stephan Tippelt, Christof Kramm, Andrew M. Donson, Adam L. Green, Chris Jones, Jens Schittenhelm, Martin Ebinger, Martin U. Schuhmann, Barbara C. Jones, Cornelis M. Tilburg, Andrea Wittmann, Andrey Golanov, Marina Ryzhova, Jonas Ecker, Till Milde, Olaf Witt, Felix Sahm, David Reuss, David Sumerauer, Josef Zamecnik, Andrey Korshunov, Andreas Deimling, Stefan M. Pfister and David T. W. Jones ()
Additional contact information
Maximilian Y. Deng: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
Dominik Sturm: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
Elke Pfaff: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
Martin Sill: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
Damian Stichel: Heidelberg University Hospital
Gnana Prakash Balasubramanian: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
Stephan Tippelt: Essen University Hospital
Christof Kramm: University Medical Center Goettingen
Andrew M. Donson: University of Colorado School of Medicine
Adam L. Green: University of Colorado School of Medicine
Chris Jones: The Institute of Cancer Research
Jens Schittenhelm: Tübingen University Hospital
Martin Ebinger: Children’s University Hospital
Martin U. Schuhmann: Tübingen University Hospital
Barbara C. Jones: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
Cornelis M. Tilburg: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
Andrea Wittmann: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
Andrey Golanov: NN Burdenko Neurosurgical Institute
Marina Ryzhova: NN Burdenko Neurosurgical Institute
Jonas Ecker: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
Till Milde: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
Olaf Witt: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
Felix Sahm: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
David Reuss: Heidelberg University Hospital
David Sumerauer: Motol University Hospital, Charles University
Josef Zamecnik: Motol University Hospital, Charles University
Andrey Korshunov: Heidelberg University Hospital
Andreas Deimling: Heidelberg University Hospital
Stefan M. Pfister: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)
David T. W. Jones: Heidelberg University Hospital and German Cancer Resarch Center (DKFZ)

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-25708-y

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