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000180591 1001_ $$00000-0002-7654-6208$$aDubois, Frank P B$$b0
000180591 245__ $$aStructural variants shape driver combinations and outcomes in pediatric high-grade glioma.
000180591 260__ $$aLondon$$bNature Research$$c2022
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000180591 500__ $$a2022 Aug;3(8):994-1011
000180591 520__ $$aWe analyzed the contributions of structural variants (SVs) to gliomagenesis across 179 pediatric high-grade gliomas (pHGGs). The most recurrent SVs targeted MYC isoforms and receptor tyrosine kinases (RTKs), including an SV amplifying a MYC enhancer in 12% of diffuse midline gliomas (DMG), indicating an underappreciated role for MYC in pHGG. SV signature analysis revealed that tumors with simple signatures were TP53 wild type (TP53WT) but showed alterations in TP53 pathway members PPM1D and MDM4. Complex signatures were associated with direct aberrations in TP53, CDKN2A and RB1 early in tumor evolution and with later-occurring extrachromosomal amplicons. All pHGGs exhibited at least one simple-SV signature, but complex-SV signatures were primarily restricted to subsets of H3.3K27M DMGs and hemispheric pHGGs. Importantly, DMGs with complex-SV signatures were associated with shorter overall survival independent of histone mutation and TP53 status. These data provide insight into the impact of SVs on gliomagenesis and the mechanisms that shape them.
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000180591 7001_ $$aShapira, Ofer$$b1
000180591 7001_ $$00000-0002-7836-4379$$aGreenwald, Noah F$$b2
000180591 7001_ $$aZack, Travis$$b3
000180591 7001_ $$aWala, Jeremiah$$b4
000180591 7001_ $$00000-0003-0540-4330$$aTsai, Jessica W$$b5
000180591 7001_ $$aCrane, Alexander$$b6
000180591 7001_ $$00000-0001-8011-2341$$aBaguette, Audrey$$b7
000180591 7001_ $$aHadjadj, Djihad$$b8
000180591 7001_ $$00000-0002-9050-9315$$aHarutyunyan, Ashot S$$b9
000180591 7001_ $$aKumar, Kiran H$$b10
000180591 7001_ $$0P:(DE-He78)261d2b84aded878003e6e35d18113831$$aBlattner-Johnson, Mirjam$$b11$$udkfz
000180591 7001_ $$aVogelzang, Jayne$$b12
000180591 7001_ $$aSousa, Cecilia$$b13
000180591 7001_ $$aKang, Kyung Shin$$b14
000180591 7001_ $$aSinai, Claire$$b15
000180591 7001_ $$00000-0002-2185-1782$$aWang, Dayle K$$b16
000180591 7001_ $$aKhadka, Prasidda$$b17
000180591 7001_ $$aLewis, Kathleen$$b18
000180591 7001_ $$aNguyen, Lan$$b19
000180591 7001_ $$aMalkin, Hayley$$b20
000180591 7001_ $$00000-0002-4622-8188$$aHo, Patricia$$b21
000180591 7001_ $$aO'Rourke, Ryan$$b22
000180591 7001_ $$aZhang, Shu$$b23
000180591 7001_ $$aGold, Rose$$b24
000180591 7001_ $$aDeng, Davy$$b25
000180591 7001_ $$aSerrano, Jonathan$$b26
000180591 7001_ $$aSnuderl, Matija$$b27
000180591 7001_ $$aJones, Chris$$b28
000180591 7001_ $$aWright, Karen D$$b29
000180591 7001_ $$aChi, Susan N$$b30
000180591 7001_ $$aGrill, Jacques$$b31
000180591 7001_ $$00000-0002-5158-7126$$aKleinman, Claudia L$$b32
000180591 7001_ $$00000-0002-2662-719X$$aGoumnerova, Liliana C$$b33
000180591 7001_ $$00000-0003-2485-3692$$aJabado, Nada$$b34
000180591 7001_ $$0P:(DE-He78)551bb92841f634070997aa168d818492$$aJones, David$$b35$$udkfz
000180591 7001_ $$aKieran, Mark W$$b36
000180591 7001_ $$00000-0002-7733-600X$$aLigon, Keith L$$b37
000180591 7001_ $$00000-0001-6303-3609$$aBeroukhim, Rameen$$b38
000180591 7001_ $$00000-0002-4175-4760$$aBandopadhayay, Pratiti$$b39
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