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

当前位置： X-MOL 学术 › Cancer Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.
Cancer Cell ( IF 48.8 ) Pub Date : 2017-10-09 , DOI: 10.1016/j.ccell.2017.08.017
Alan Mackay ₁ , Anna Burford ₁ , Diana Carvalho ₁ , Elisa Izquierdo ₁ , Janat Fazal-Salom ₁ , Kathryn R Taylor ₂ , Lynn Bjerke ₁ , Matthew Clarke ₁ , Mara Vinci ₁ , Meera Nandhabalan ₁ , Sara Temelso ₁ , Sergey Popov ₃ , Valeria Molinari ₁ , Pichai Raman ₄ , Angela J Waanders ₅ , Harry J Han ₅ , Saumya Gupta ₆ , Lynley Marshall ₇ , Stergios Zacharoulis ₇ , Sucheta Vaidya ₇ , Henry C Mandeville ₈ , Leslie R Bridges ₉ , Andrew J Martin ₁₀ , Safa Al-Sarraj ₁₁ , Christopher Chandler ₁₂ , Ho-Keung Ng ₁₃ , Xingang Li ₁₄ , Kun Mu ₁₅ , Saoussen Trabelsi ₁₆ , Dorra H'mida-Ben Brahim ₁₆ , Alexei N Kisljakov ₁₇ , Dmitry M Konovalov ₁₈ , Andrew S Moore ₁₉ , Angel Montero Carcaboso ₂₀ , Mariona Sunol ₂₀ , Carmen de Torres ₂₀ , Ofelia Cruz ₂₀ , Jaume Mora ₂₀ , Ludmila I Shats ₂₁ , João N Stavale ₂₂ , Lucas T Bidinotto ₂₃ , Rui M Reis ₂₄ , Natacha Entz-Werle ₂₅ , Michael Farrell ₂₆ , Jane Cryan ₂₆ , Darach Crimmins ₂₇ , John Caird ₂₇ , Jane Pears ₂₈ , Michelle Monje ₂₉ , Marie-Anne Debily ₃₀ , David Castel ₃₀ , Jacques Grill ₃₀ , Cynthia Hawkins ₃₁ , Hamid Nikbakht ₃₂ , Nada Jabado ₃₃ , Suzanne J Baker ₃₄ , Stefan M Pfister ₃₅ , David T W Jones ₃₆ , Maryam Fouladi ₃₇ , André O von Bueren ₃₈ , Michael Baudis ₆ , Adam Resnick ₃₉ , Chris Jones ₁

Affiliation

Division of Molecular Pathology, The Institute of Cancer Research, London, UK; Division of Cancer Therapeutics, The Institute of Cancer Research, London, UK.
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.
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.
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.
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.
Institute of Molecular Life Sciences, Swiss Institute of Bioinformatics, University of Zürich, Zürich, Switzerland.
Pediatric Oncology Drug Development Team, Children and Young People's Unit, Royal Marsden Hospital, Sutton, UK.
Department of Radiotherapy, Royal Marsden Hospital, Sutton, UK.
Department of Cellular Pathology, St George's Hospital NHS Trust, London, UK.
Department of Neurosurgery, St George's Hospital NHS Trust, London, UK.
Department of Neuropathology, Kings College Hospital, London, UK.
Department of Neurosurgery, Kings College Hospital, London, UK.
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China.
Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan, China.
Department of Pathology, Shandong University School of Medicine, Jinan, China.
Department of Cytogenetics and Reproductive Biology, Farhat Hached Hospital, Sousse, Tunisia.
Department of Pathology, Morozov Children's Hospital, Moscow, Russian Federation.
Department of Pathology, Dmitrii Rogachev Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russian Federation.
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.
Institut de Recerca Sant Joan de Deu, Barcelona, Spain.
Division of Oncology, Pediatric Oncology and Radiotherapy, St Petersburg State Pediatric Medical University, St Petersburg, Russian Federation.
Department of Pathology, Federal University of São Paulo, São Paulo, São Paulo, Brazil.
Molecular Oncology Research Centre, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
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.
Pédiatrie Onco-Hématologie - Pédiatrie III, Centre Hospitalier Régional et Universitaire Hautepierre, Strasbourg, France.
Histopathology Department, Beaumont Hospital, Dublin, Ireland.
Department of Neurosurgery, Temple Street Children's University Hospital, Dublin, Ireland.
Department of Paediatric Oncology, Our Lady's Children's Hospital, Dublin, Ireland.
Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.
Département de Cancerologie de l'Enfant et de l'Adolescent, Institut Gustav Roussy, Villejuif, France.
Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Canada.
Department of Pediatrics, McGill University, Montreal, Canada.
The Center for Data Driven Discovery in Biomedicine (D(3)b), Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, TN, USA.
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.
Division of Pediatric Neuro-oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg, Germany.
Department of Pediatrics, Cancer and Blood Diseases Institute, Cincinnati Children's Hospital, Cincinnati, OH, USA.
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.
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.

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.

中文翻译：

对 1,000 例儿童高级别和弥漫性内源性脑桥胶质瘤的综合分子荟萃分析。

我们整理了 157 例未发表的儿科高级别胶质瘤和弥漫性内源性脑桥胶质瘤病例的数据以及 20 个公开数据集，对超过 1,000 例病例进行了综合分析。我们在组蛋白突变亚组中发现了共分离突变，包括 H3.3G34R/V 中 FBXW7 的缺失、H3.3K27M 中的 TOP3A 重排以及 H3.1K27M 中的 BCOR 突变。组蛋白野生型亚组通过关键致癌事件或更接近低级别肿瘤的甲基化谱的存在而得到完善。基因组畸变随着年龄的增长而增加，凸显了婴儿群体在生物学和临床上的独特性。在一小部分肿瘤中发现了罕见的通路失调，进一步定义了疾病的分子多样性，为生物学研究开辟了途径，并为功能定义的未来治疗分层提供了基础。

更新日期：2017-09-29

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11