Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.
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Date
2017-10-09Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of 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.
Subject
Humans
Glioma
Brain Stem Neoplasms
DNA Topoisomerases, Type I
Ubiquitin-Protein Ligases
F-Box Proteins
Cell Cycle Proteins
Proto-Oncogene Proteins
Histones
Repressor Proteins
Gene Dosage
Mutation
Adolescent
Child
Child, Preschool
Infant
Infant, Newborn
Female
Male
Young Adult
Exome
F-Box-WD Repeat-Containing Protein 7
Research team
Glioma Team
Paediatric and Adolescent Radiotherapy
Language
eng
Date accepted
2017-08-29
License start date
2017-10
Citation
Cancer cell, 2017, 32 (4), pp. 520 - 537.e5
Publisher
CELL PRESS
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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