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

Author(s):Show less -

Mackay, Alan ^{[1, 2]} ; Burford, Anna ^{[1, 2]} ; Carvalho, Diana ^{[1, 2]} ; Izquierdo, Elisa ^{[1, 2]} ; Fazal-Salom, Janat ^{[1, 2]} ; Taylor, Kathryn R. ^{[1, 2, 3]} ; Bjerke, Lynn ^{[1, 2]} ; Clarke, Matthew ^{[1, 2]} ; Vinci, Mara ^{[1, 2]} ; Nandhabalan, Meera ^{[1, 2]} ; Temelso, Sara ^{[1, 2]} ; Popov, Sergey ^{[1, 2, 4]} ; Molinari, Valeria ^{[1, 2]} ; Raman, Pichai ^{[5, 6]} ; Waanders, Angela J. ^{[5, 7]} ; Han, Harry J. ^{[5, 7]} ; Gupta, Saumya ^[8] ; Marshall, Lynley ^[9] ; Zacharoulis, Stergios ^[9] ; Vaidya, Sucheta ^[9] ; Mandeville, Henry C. ^[10] ; Bridges, Leslie R. ^[11] ; Martin, Andrew J. ^[12] ; Al-Sarraj, Safa ^[13] ; Chandler, Christopher ^[14] ; Ng, Ho-Keung ^[15] ; Li, Xingang ^{[16, 17]} ; Mu, Kun ^[18] ; Trabelsi, Saoussen ^[19] ; H'mida-Ben Brahim, Dorra ; Kisljakov, Alexei N. ^[20] ; Konovalov, Dmitry M. ^[21] ; Moore, Andrew S. ^{[22, 23, 24]} ; Montero Carcaboso, Angel ^[25] ; Sunol, Mariona ^[25] ; de Torres, Carmen ^[25] ; Cruz, Ofelia ^[25] ; Mora, Jaume ^[25] ; Shats, Ludmila I. ^[26] ; Stavale, Joao N. ^[27] ; Bidinotto, Lucas T. ^[28] ; Reis, Rui M. ^{[29, 28, 30]} ; Entz-Werle, Natacha ^{[31, 32]} ; Farrell, Michael ^[33] ; Cryan, Jane ^[33] ; Crimmins, Darach ^[34] ; Caird, John ^[34] ; Pears, Jane ^[35] ; Monje, Michelle ^[3] ; Debily, Marie-Anne ^[36] ; Castel, David ^[36] ; Grill, Jacques ^[36] ; Hawkins, Cynthia ^[37] ; Nikbakht, Hamid ^[38] ; Jabado, Nada ; Baker, Suzanne J. ^[39] ; Pfister, Stefan M. ^{[40, 41, 42]} ; Jones, David T. W. ^{[40, 42]} ; Fouladi, Maryam ^[43] ; von Bueren, Andre O. ^{[44, 45, 46]} ; Baudis, Michael ^[8] ; Resnick, Adam ^{[5, 6, 7]} ; Jones, Chris ^{[1, 2]}

Affiliation:Show less -

^[1] Inst Canc Res, Div Mol Pathol, London - England

^[2] Inst Canc Res, Div Canc Therapeut, London - England

^[3] Stanford Univ, Sch Med, Dept Neurol, Stanford, CA - USA

^[4] Univ Hosp Wales, Dept Cellular Pathol, Cardiff, S Glam - Wales

^[5] Childrens Hosp Philadelphia, Ctr Data Driven Discovery Biomed D3b, Philadelphia, PA - USA

^[6] Childrens Hosp Philadelphia, Div Neurosurg, Philadelphia, PA - USA

^[7] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA - USA

^[8] Univ Zurich, Swiss Inst Bioinformat, Inst Mol Life Sci, Zurich - Switzerland

^[9] Royal Marsden Hosp, Children & Young Peoples Unit, Pediat Oncol Drug Dev Team, Sutton, Surrey - England

^[10] Royal Marsden Hosp, Dept Radiotherapy, Sutton, Surrey - England

^[11] St Georges Hosp NHS Trust, Dept Cellular Pathol, London - England

^[12] St Georges Hosp NHS Trust, Dept Neurosurg, London - England

^[13] Kings Coll Hosp London, Dept Neuropathol, London - England

^[14] Kings Coll Hosp London, Dept Neurosurg, London - England

^[15] Chinese Univ Hong Kong, Dept Anat & Cellular Pathol, Hong Kong, Hong Kong - Peoples R China

^[16] Shandong Univ, Qilu Hosp, Dept Neurosurg, Jinan, Shandong - Peoples R China

^[17] Shandong Univ, Brain Sci Res Inst, Jinan, Shandong - Peoples R China

^[18] Shandong Univ, Sch Med, Dept Pathol, Jinan, Shandong - Peoples R China

^[19] Farhat Hached Hosp, Dept Cytogenet & Reprod Biol, Sousse - Tunisia

^[20] Morozov Childrens Hosp, Dept Pathol, Moscow - Russia

^[21] Dmitrii Rogachev Res & Clin Ctr Pediat Hematol On, Dept Pathol, Moscow - Russia

^[22] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld - Australia

^[23] Univ Queensland, UQ Child Hlth Res Ctr, Brisbane, Qld - Australia

^[24] Childrens Hlth Queensland Hosp & Hlth Serv, Oncol Serv Grp, Brisbane, Qld - Australia

^[25] Inst Recerca Sant Joan de Deu, Barcelona - Spain

^[26] St Petersburg State Pediat Med Univ, Div Oncol Pediat Oncol & Radiotherapy, St Petersburg - Russia

^[27] Univ Fed Sao Paulo, Dept Pathol, Sao Paulo, SP - Brazil

^[28] Barretos Canc Hosp, Mol Oncol Res Ctr, Sao Paulo - Brazil

^[29] ICVS 3Bs PT Govt Associate Lab, Braga - Portugal

^[30] Univ Minho, Med Sch, Life & Hlth Sci Res Inst ICVS, Braga - Portugal

^[31] Ctr Hosp Reg, Pediat Oncohemato Pediat 3, Strasbourg - France

^[32] Univ Hautepierre, Strasbourg - France

^[33] Beaumont Hosp, Histopathol Dept, Dublin - Ireland

^[34] Temple St Childrens Univ Hosp, Dept Neurosurg, Dublin - Ireland

^[35] Our Ladys Childrens Hosp, Dept Paediat Oncol, Dublin - Ireland

^[36] Inst Gustav Roussy, Dept Cancerol Enfant & Adolescent, Villejuif - France

^[37] Hosp Sick Children, Pediat Lab Med, Toronto, ON - Canada

^[38] McGill Univ, Dept Pediat, Montreal, PQ - Canada

^[39] St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN - USA

^[40] German Canc Res Ctr, Div Pediat Neurooncol, Heidelberg - Germany

^[41] Univ Heidelberg Hosp, Dept Pediat Hematol & Oncol, Heidelberg - Germany

^[42] NCT Heidelberg KiTZ, Hopp Childrens Canc Ctr, Heidelberg - Germany

^[43] Cincinnati Childrens Hosp, Canc & Blood Dis Inst, Dept Pediat, Cincinnati, OH - USA

^[44] Univ Med Ctr Goettingen, Div Pediat Hematol & Oncol, Dept Pediat, Gottingen - Germany

^[45] Univ Hosp Geneva, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med, Geneva - Switzerland

^[46] Univ Geneva, Fac Med, CANSEARCH Res Lab, Dept Pediat, Geneva - Switzerland

• Document type: Journal article
• Source: CANCER CELL; v. 32, n. 4, p. 520+, OCT 9 2017.
• Web of Science Citations: 115

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. (AU)

• FAPESP's process: 11/08523-7 - Chromosomal alterations profiling in brain tumors (medulloblastomas and gliomas): the impact in the identification of new tumorigenic pathways
• Grantee: Lucas Tadeu Bidinotto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/08287-4 - Chromosomal alterations profiling in gliomas
• Grantee: Lucas Tadeu Bidinotto
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor