دورية أكاديمية
Structural variants shape driver combinations and outcomes in pediatric high-grade glioma.
| العنوان: | Structural variants shape driver combinations and outcomes in pediatric high-grade glioma. |
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| المؤلفون: | Dubois, FPB, Shapira, O, Greenwald, NF, Zack, T, Wala, J, Tsai, JW, Crane, A, Baguette, A, Hadjadj, D, Harutyunyan, AS, Kumar, KH, Blattner-Johnson, M, Vogelzang, J, Sousa, C, Kang, KS, Sinai, C, Wang, DK, Khadka, P, Lewis, K, Nguyen, L, Malkin, H, Ho, P, O'Rourke, R, Zhang, S, Gold, R, Deng, D, Serrano, J, Snuderl, M, Jones, C, Wright, KD, Chi, SN, Grill, J, Kleinman, CL, Goumnerova, LC, Jabado, N, Jones, DTW, Kieran, MW, Ligon, KL, Beroukhim, R, Bandopadhayay, P |
| المساهمون: | Jones, Chris |
| بيانات النشر: | OXFORD UNIV PRESS INC |
| سنة النشر: | 2022 |
| المجموعة: | The Institute of Cancer Research (ICR): Publications Repository |
| مصطلحات موضوعية: | Brain Neoplasms, Cell Cycle Proteins, Child, Glioma, Histones, Humans, Mutation, Proto-Oncogene Proteins |
| جغرافية الموضوع: | England |
| الوصف: | We 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; 1011; application/pdf |
| اللغة: | English |
| تدمد: | 2662-1347 |
| العلاقة: | Nature Cancer, 2022, 3 (8), pp. 994 - 1011; https://repository.icr.ac.uk/handle/internal/5509Test |
| DOI: | 10.1038/s43018-022-00403-z |
| الإتاحة: | https://doi.org/10.1038/s43018-022-00403-zTest https://repository.icr.ac.uk/handle/internal/5509Test |
| حقوق: | http://www.rioxx.net/licenses/all-rights-reservedTest |
| رقم الانضمام: | edsbas.4431B470 |
| قاعدة البيانات: | BASE |
| تدمد: | 26621347 |
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| DOI: | 10.1038/s43018-022-00403-z |