Format

Send to

Choose Destination
Cancer Cell. 2017 Oct 9;32(4):520-537.e5. doi: 10.1016/j.ccell.2017.08.017. Epub 2017 Sep 28.

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

Author information

1
Division of Molecular Pathology, The Institute of Cancer Research, London, UK; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.
2
Division of Molecular Pathology, The Institute of Cancer Research, London, UK; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK; Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.
3
Division of Molecular Pathology, The Institute of Cancer Research, London, UK; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK; Department of Cellular Pathology, University Hospital of Wales, Cardiff, UK.
4
The Center for Data Driven Discovery in Biomedicine (D(3)b), Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
5
The Center for Data Driven Discovery in Biomedicine (D(3)b), Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
6
Institute of Molecular Life Sciences, Swiss Institute of Bioinformatics, University of Zürich, Zürich, Switzerland.
7
Pediatric Oncology Drug Development Team, Children and Young People's Unit, Royal Marsden Hospital, Sutton, UK.
8
Department of Radiotherapy, Royal Marsden Hospital, Sutton, UK.
9
Department of Cellular Pathology, St George's Hospital NHS Trust, London, UK.
10
Department of Neurosurgery, St George's Hospital NHS Trust, London, UK.
11
Department of Neuropathology, Kings College Hospital, London, UK.
12
Department of Neurosurgery, Kings College Hospital, London, UK.
13
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China.
14
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, China.
15
Department of Pathology, Shandong University School of Medicine, Jinan, China.
16
Department of Cytogenetics and Reproductive Biology, Farhat Hached Hospital, Sousse, Tunisia.
17
Department of Pathology, Morozov Children's Hospital, Moscow, Russian Federation.
18
Department of Pathology, Dmitrii Rogachev Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.
19
UQ Child Health Research Centre, The University of Queensland, Brisbane, Australia; Oncology Services Group, Children's Health Queensland Hospital and Health Service, Brisbane, Australia; The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia.
20
Institut de Recerca Sant Joan de Deu, Barcelona, Spain.
21
Division of Oncology, Pediatric Oncology and Radiotherapy, St Petersburg State Pediatric Medical University, St Petersburg, Russian Federation.
22
Department of Pathology, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
23
Molecular Oncology Research Centre, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
24
Molecular Oncology Research Centre, Barretos Cancer Hospital, Barretos, São Paulo, Brazil; Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal and ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
25
Pédiatrie Onco-Hématologie - Pédiatrie III, Centre Hospitalier Régional et Universitaire Hautepierre, Strasbourg, France.
26
Histopathology Department, Beaumont Hospital, Dublin, Ireland.
27
Department of Neurosurgery, Temple Street Children's University Hospital, Dublin, Ireland.
28
Department of Paediatric Oncology, Our Lady's Children's Hospital, Dublin, Ireland.
29
Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.
30
Département de Cancerologie de l'Enfant et de l'Adolescent, Institut Gustav Roussy, Villejuif, France.
31
Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada.
32
Department of Pediatrics, McGill University, Montreal, Canada.
33
The Center for Data Driven Discovery in Biomedicine (D(3)b), Children's Hospital of Philadelphia, Philadelphia, PA, USA.
34
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA.
35
Division of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany; Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
36
Division of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
37
Department of Pediatrics, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital, Cincinnati, OH, USA.
38
Department of Pediatrics, Division of Pediatric Hematology and Oncology, University Medical Center Goettingen, Goettingen, Germany; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Hospital of Geneva, Geneva, Switzerland; Department of Pediatrics, CANSEARCH Research Laboratory, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
39
The Center for Data Driven Discovery in Biomedicine (D(3)b), Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Neurosurgery, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
40
Division of Molecular Pathology, The Institute of Cancer Research, London, UK; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK. Electronic address: chris.jones@icr.ac.uk.

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.

KEYWORDS:

DIPG; exome; genome; glioblastoma; histone; methylation

PMID:
28966033
PMCID:
PMC5637314
DOI:
10.1016/j.ccell.2017.08.017
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center