Dataset Information

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

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.

SUBMITTER: Deng MY

PROVIDER: S-EPMC8452680 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

Deng Maximilian Y MY Sturm Dominik D Pfaff Elke E Sill Martin M Stichel Damian D Balasubramanian Gnana Prakash GP Tippelt Stephan S Kramm Christof C Donson Andrew M AM Green Adam L AL Jones Chris C Schittenhelm Jens J Ebinger Martin M Schuhmann Martin U MU Jones Barbara C BC van Tilburg Cornelis M CM Wittmann Andrea A Golanov Andrey A Ryzhova Marina M Ecker Jonas J Milde Till T Witt Olaf O Sahm Felix F Reuss David D Sumerauer David D Zamecnik Josef J Korshunov Andrey A von Deimling Andreas A Pfister Stefan M SM Jones David T W DTW

Nature communications 20210920 1

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 o ...[more]

PMID: 34545083

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Project description:BackgroundThe 2016 World Health Organization (WHO) classification of central nervous system tumors stratifies isocitrate dehydrogenase (IDH)-mutant gliomas into 2 major groups depending on the presence or absence of 1p/19q codeletion. However, the grading system remains unchanged and it is now controversial whether it can be still applied to this updated molecular classification.MethodsIn a large cohort of 911 high-grade IDH-mutant gliomas from the French national POLA network (including 428 IDH-mutant gliomas without 1p/19q codeletion and 483 anaplastic oligodendrogliomas, IDH-mutant and 1p/19q codeleted), we investigated the prognostic value of the cyclin-dependent kinase inhibitor 2A (CDKN2A) gene homozygous deletion as well as WHO grading criteria (mitoses, microvascular proliferation, and necrosis). In addition, we searched for other retinoblastoma pathway gene alterations (CDK4 amplification and RB1 homozygous deletion) in a subset of patients. CDKN2A homozygous deletion was also searched in an independent series of 40 grade II IDH-mutant gliomas.ResultsCDKN2A homozygous deletion was associated with dismal outcome among IDH-mutant gliomas lacking 1p/19q codeletion (P < 0.0001 for progression-free survival and P = 0.004 for overall survival) as well as among anaplastic oligodendrogliomas, IDH-mutant + 1p/19q codeleted (P = 0.002 for progression-free survival and P < 0.0001 for overall survival) in univariate and multivariate analysis including age, extent of surgery, adjuvant treatment, microvascular proliferation, and necrosis. In both groups, the presence of microvascular proliferation and/or necrosis remained of prognostic value only in cases lacking CDKN2A homozygous deletion. CDKN2A homozygous deletion was not recorded in grade II gliomas.ConclusionsOur study pointed out the utmost relevance of CDKN2A homozygous deletion as an adverse prognostic factor in the 2 broad categories of IDH-mutant gliomas stratified on 1p/19q codeletion and suggests that the grading of these tumors should be refined.

Dataset Information

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

Publications

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

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