Supplementary Table S7 from Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes

dataset

posted on 2023-04-03, 22:24 authored by Matthew Clarke, Alan Mackay, Britta Ismer, Jessica C. Pickles, Ruth G. Tatevossian, Scott Newman, Tejus A. Bale, Iris Stoler, Elisa Izquierdo, Sara Temelso, Diana M. Carvalho, Valeria Molinari, Anna Burford, Louise Howell, Alex Virasami, Amy R. Fairchild, Aimee Avery, Jane Chalker, Mark Kristiansen, Kelly Haupfear, James D. Dalton, Wilda Orisme, Ji Wen, Michael Hubank, Kathreena M. Kurian, Catherine Rowe, Mellissa Maybury, Stephen Crosier, Jeffrey Knipstein, Ulrich Schüller, Uwe Kordes, David E. Kram, Matija Snuderl, Leslie Bridges, Andrew J. Martin, Lawrence J. Doey, Safa Al-Sarraj, Christopher Chandler, Bassel Zebian, Claire Cairns, Rachael Natrajan, Jessica K.R. Boult, Simon P. Robinson, Martin Sill, Ira J. Dunkel, Stephen W. Gilheeney, Marc K. Rosenblum, Debbie Hughes, Paula Z. Proszek, Tobey J. Macdonald, Matthias Preusser, Christine Haberler, Irene Slavc, Roger Packer, Ho-Keung Ng, Shani Caspi, Mara Popović, Barbara Faganel Kotnik, Matthew D. Wood, Lissa Baird, Monika Ashok Davare, David A. Solomon, Thale Kristin Olsen, Petter Brandal, Michael Farrell, Jane B. Cryan, Michael Capra, Michael Karremann, Jens Schittenhelm, Martin U. Schuhmann, Martin Ebinger, Winand N.M. Dinjens, Kornelius Kerl, Simone Hettmer, Torsten Pietsch, Felipe Andreiuolo, Pablo Hernáiz Driever, Andrey Korshunov, Lotte Hiddingh, Barbara C. Worst, Dominik Sturm, Marc Zuckermann, Olaf Witt, Tabitha Bloom, Clare Mitchell, Evelina Miele, Giovanna Stefania Colafati, Francesca Diomedi-Camassei, Simon Bailey, Andrew S. Moore, Timothy E.G. Hassall, Stephen P. Lowis, Maria Tsoli, Mark J. Cowley, David S. Ziegler, Matthias A. Karajannis, Kristian Aquilina, Darren R. Hargrave, Fernando Carceller, Lynley V. Marshall, Andreas von Deimling, Christof M. Kramm, Stefan M. Pfister, Felix Sahm, Suzanne J. Baker, Angela Mastronuzzi, Andrea Carai, Maria Vinci, David Capper, Sergey Popov, David W. Ellison, Thomas S. Jacques, David T.W. Jones, Chris Jones

Supplementary Table S7

Funding

CRIS Cancer Foundation

INSTINCT network

Brain Tumour Charity

Great Ormond Street Children's Charity

Children with Cancer UK

Cancer Research UK

National Institute for Health Research Biomedical Research Centre

NIHR Great Ormond Street Hospital Biomedical Research Centre

Experimental Cancer Medicines Centre

Paediatric Network

CRUK

MRC

Department of Health

German Children's Cancer Foundation

German Cancer Aid

German Federal Ministry of Education and Research

Cure Brain Cancer Foundation

Australian Lions Childhood Cancer Research Foundation

Lions Club International Foundation

American, Lebanese and Syrian-Associated Charities

Children's Hospital Foundation

Marie-Josée and Henry R. Kravis Center for Molecular Oncology

National Cancer Institute

Friedberg Charitable Foundation

Making Headway Foundation

Sohn Conference Foundation

Helmholtz Association Research Grant

NIH

History

ARTICLE ABSTRACT

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an “intrinsic” spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of ALK, NTRK1/2/3, ROS1, or MET gene fusions. Kinase fusion–positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype.See related video: https://vimeo.com/438254885See related commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890

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Keywords

Cns Cancers Gliomas, Glioblastomas Pediatric Cancers Small Molecule Agents Kinase inhibitors

Licence

CC BY

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