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Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

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Publication Date
2017-10-09
ICR Author
Jones, Chris
Mandeville, Henry
Molinari, Valeria
Fazal Salom, Janat
Bjerke, Lynn
Marsden,
Author
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
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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We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of 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.
URL
https://repository.icr.ac.uk/handle/internal/991
Collections
  • Cancer Therapeutics
  • Molecular Pathology
  • Radiotherapy and Imaging
Licenseref URL
http://www.rioxx.net/licenses/under-embargo-all-rights-reserved
Funder
The Institute of Cancer Research (Grant ID: Unspecified)
Version of record
10.1016/j.ccell.2017.08.017
Subject
DIPG
exome
genome
glioblastoma
histone
methylation
Adolescent
Brain Stem Neoplasms
Cell Cycle Proteins
Child
Child, Preschool
DNA Topoisomerases, Type I
Exome
F-Box Proteins
F-Box-WD Repeat-Containing Protein 7
Female
Gene Dosage
Glioma
Histones
Humans
Infant
Infant, Newborn
Male
Mutation
Proto-Oncogene Proteins
Repressor Proteins
Ubiquitin-Protein Ligases
Young Adult
Research team
Glioma Team
Radiotherapy for Children, Teenagers and Young Adults
Language
eng
Date accepted
2017-08-29
License start date
2017-10-09
Citation
Cancer Cell, 2017, 32 (4), pp. 520 - 537.e5

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