Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B.
Maximilian Y DengDominik SturmElke PfaffMartin SillDamian StichelGnana Prakash BalasubramanianStephan TippeltChristof KrammAndrew M DonsonAdam L GreenChris JonesCornelia BrendleMartin EbingerMartin U SchuhmannBarbara C JonesCornelis M van TilburgAndrea WittmannAndrey GolanovMarina RyzhovaJonas EckerTill MildeOlaf WittFelix SahmDavid ReussDavid SumerauerJosef ZamecnikAndrey KorshunovAndreas von DeimlingStefan M PfisterDavid T W JonesPublished in: Nature communications (2021)
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.
Keyphrases
- radiation induced
- radiation therapy
- end stage renal disease
- acute lymphoblastic leukemia
- wild type
- chronic kidney disease
- high grade
- newly diagnosed
- ejection fraction
- genome wide
- low grade
- copy number
- risk factors
- squamous cell carcinoma
- patient reported outcomes
- transcription factor
- allogeneic hematopoietic stem cell transplantation