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

被引：32

作者：

Deng, Maximilian Y. ^{[1
,2
,3
]}

Sturm, Dominik ^{[1
,2
,3
,4
]}

Pfaff, Elke ^{[1
,2
,3
,4
]}

Sill, Martin ^{[1
,2
,5
,6
]}

Stichel, Damian ^{[6
,7
,8
]}

Balasubramanian, Gnana Prakash ^{[1
,2
,5
,6
]}

Tippelt, Stephan ^{[9
]}

Kramm, Christof ^{[10
]}

Donson, Andrew M. ^{[11
]}

Green, Adam L. ^{[11
]}

Jones, Chris ^{[12
,13
]}

Schittenhelm, Jens ^{[14
,15
]}

Ebinger, Martin ^{[16
]}

Schuhmann, Martin U. ^{[17
]}

Jones, Barbara C. ^{[1
,2
,3
,4
]}

van Tilburg, Cornelis M. ^{[1
,2
,4
,6
,18
]}

Wittmann, Andrea ^{[1
,2
,3
]}

Golanov, Andrey ^{[19
]}

Ryzhova, Marina ^{[19
]}

Ecker, Jonas ^{[1
,2
,4
,6
,18
]}

Milde, Till ^{[1
,2
,4
,6
,18
]}

Witt, Olaf ^{[1
,2
,4
,6
,18
]}

Sahm, Felix ^{[1
,2
,6
,7
,8
]}

Reuss, David ^{[6
,7
,8
]}

Sumerauer, David ^{[20
]}

Zamecnik, Josef ^{[21
]}

Korshunov, Andrey ^{[6
,7
,8
]}

von Deimling, Andreas ^{[6
,7
,8
]}

Pfister, Stefan M. ^{[1
,2
,4
,5
,6
]}

Jones, David T. W. ^{[1
,2
,3
]}

机构：

[1] Heidelberg Univ Hosp, Hopp Childrens Canc Ctr Heidelberg KiTZ, Heidelberg, Germany

[2] German Canc Res Ctr, Heidelberg, Germany

[3] German Canc Res Ctr, Div Pediat Glioma Res, Heidelberg, Germany

[4] Heidelberg Univ Hosp, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany

[5] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg, Germany

[6] German Consortium Translat Canc Res DKTK, Heidelberg, Germany

[7] Heidelberg Univ Hosp, Inst Pathol, Dept Neuropathol, Heidelberg, Germany

[8] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, Heidelberg, Germany

[9] Essen Univ Hosp, Dept Pediat Oncol & Hematol, Essen, Germany

[10] Univ Med Ctr Goettingen, Div Pediat Hematol & Oncol, Gottingen, Germany

[11] Univ Colorado, Morgan Adams Fdn, Dept Pediat, Pediat Brain Tumor Res Program,Sch Med, Aurora, CO USA

[12] Inst Canc Res, Div Mol Pathol, London, England

[13] Inst Canc Res, Div Canc Therapeut, London, England

[14] Tubingen Univ Hosp, Inst Pathol & Neuropathol, Dept Neuropathol, Tubingen, Germany

[15] Tubingen Univ Hosp, Comprehens Canc Ctr Tubingen Stuttgart, Tubingen, Germany

[16] Childrens Univ Hosp, Dept Pediat Hematol Oncol, Tubingen, Germany

[17] Tubingen Univ Hosp, Dept Neurosurg, Div Pediat Neurosurg, Tubingen, Germany

[18] German Canc Res Ctr, Clin Cooperat Unit Pediat Oncol, Heidelberg, Germany

[19] NN Burdenko Inst Neurosurg, Dept Neuropathol, Moscow, Russia

[20] Charles Univ Prague, Motol Univ Hosp, Dept Pediat Hematol & Oncol, Prague, Czech Republic

[21] Charles Univ Prague, Motol Univ Hosp, Dept Pathol, Prague, Czech Republic

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

CHILDHOOD-CANCER SURVIVOR; 2ND MALIGNANT NEOPLASMS; SECONDARY BRAIN-TUMORS; HIGH-GRADE GLIOMAS; MOLECULAR CHARACTERISTICS; INDUCED GLIOBLASTOMA; LATE MORTALITY; LONG-TERM; MEDULLOBLASTOMA; RISK;

D O I：

10.1038/s41467-021-25708-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies but their origin are still unclear. Here, the authors define the genomic, epigenetic and transcriptional landscape of 32 RIGs cases.

引用

页数：11

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