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

Nat Commun. 2021 Sep 20;12(1):5530. doi: 10.1038/s41467-021-25708-y.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Chromosome Deletion
  • Cluster Analysis
  • Cyclin-Dependent Kinase Inhibitor p15 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • DNA Methylation / genetics
  • Female
  • Gene Amplification*
  • Gene Expression Regulation, Neoplastic
  • Gene Rearrangement / genetics
  • Genome, Human
  • Glioma / genetics*
  • Glioma / pathology
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / pathology*
  • Radiation
  • Receptor, Platelet-Derived Growth Factor alpha / genetics*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Transcription, Genetic
  • Young Adult

Substances

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