Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.
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Authors
Mackay, A
Burford, A
Carvalho, D
Izquierdo, E
Fazal-Salom, J
Taylor, KR
Bjerke, L
Clarke, M
Vinci, M
Nandhabalan, M
Temelso, S
Popov, S
Molinari, V
Raman, P
Waanders, AJ
Han, HJ
Gupta, S
Marshall, L
Zacharoulis, S
Vaidya, S
Mandeville, HC
Bridges, LR
Martin, AJ
Al-Sarraj, S
Chandler, C
Ng, H-K
Li, X
Mu, K
Trabelsi, S
Brahim, DH-B
Kisljakov, AN
Konovalov, DM
Moore, AS
Carcaboso, AM
Sunol, M
de Torres, C
Cruz, O
Mora, J
Shats, LI
Stavale, JN
Bidinotto, LT
Reis, RM
Entz-Werle, N
Farrell, M
Cryan, J
Crimmins, D
Caird, J
Pears, J
Monje, M
Debily, M-A
Castel, D
Grill, J
Hawkins, C
Nikbakht, H
Jabado, N
Baker, SJ
Pfister, SM
Jones, DTW
Fouladi, M
von Bueren, AO
Baudis, M
Resnick, A
Jones, C
Burford, A
Carvalho, D
Izquierdo, E
Fazal-Salom, J
Taylor, KR
Bjerke, L
Clarke, M
Vinci, M
Nandhabalan, M
Temelso, S
Popov, S
Molinari, V
Raman, P
Waanders, AJ
Han, HJ
Gupta, S
Marshall, L
Zacharoulis, S
Vaidya, S
Mandeville, HC
Bridges, LR
Martin, AJ
Al-Sarraj, S
Chandler, C
Ng, H-K
Li, X
Mu, K
Trabelsi, S
Brahim, DH-B
Kisljakov, AN
Konovalov, DM
Moore, AS
Carcaboso, AM
Sunol, M
de Torres, C
Cruz, O
Mora, J
Shats, LI
Stavale, JN
Bidinotto, LT
Reis, RM
Entz-Werle, N
Farrell, M
Cryan, J
Crimmins, D
Caird, J
Pears, J
Monje, M
Debily, M-A
Castel, D
Grill, J
Hawkins, C
Nikbakht, H
Jabado, N
Baker, SJ
Pfister, SM
Jones, DTW
Fouladi, M
von Bueren, AO
Baudis, M
Resnick, A
Jones, C
Document Type
Journal Article
Date
2017-10-09
Date Accepted
2017-08-29
Abstract
We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification.
Citation
Cancer cell, 2017, 32 (4), pp. 520 - 537.e5
Source Title
Publisher
CELL PRESS
ISSN
1535-6108
eISSN
1878-3686
Research Team
Glioma Team
Paediatric and Adolescent Radiotherapy
Paediatric and Adolescent Radiotherapy