| Autor: |
Chris Jones, David T.W. Jones, Thomas S. Jacques, David W. Ellison, Sergey Popov, David Capper, Maria Vinci, Andrea Carai, Angela Mastronuzzi, Suzanne J. Baker, Felix Sahm, Stefan M. Pfister, Christof M. Kramm, Andreas von Deimling, Lynley V. Marshall, Fernando Carceller, Darren R. Hargrave, Kristian Aquilina, Matthias A. Karajannis, David S. Ziegler, Mark J. Cowley, Maria Tsoli, Stephen P. Lowis, Timothy E.G. Hassall, Andrew S. Moore, Simon Bailey, Francesca Diomedi-Camassei, Giovanna Stefania Colafati, Evelina Miele, Clare Mitchell, Tabitha Bloom, Olaf Witt, Marc Zuckermann, Dominik Sturm, Barbara C. Worst, Lotte Hiddingh, Andrey Korshunov, Pablo Hernáiz Driever, Felipe Andreiuolo, Torsten Pietsch, Simone Hettmer, Kornelius Kerl, Winand N.M. Dinjens, Martin Ebinger, Martin U. Schuhmann, Jens Schittenhelm, Michael Karremann, Michael Capra, Jane B. Cryan, Michael Farrell, Petter Brandal, Thale Kristin Olsen, David A. Solomon, Monika Ashok Davare, Lissa Baird, Matthew D. Wood, Barbara Faganel Kotnik, Mara Popović, Shani Caspi, Ho-Keung Ng, Roger Packer, Irene Slavc, Christine Haberler, Matthias Preusser, Tobey J. Macdonald, Paula Z. Proszek, Debbie Hughes, Marc K. Rosenblum, Stephen W. Gilheeney, Ira J. Dunkel, Martin Sill, Simon P. Robinson, Jessica K.R. Boult, Rachael Natrajan, Claire Cairns, Bassel Zebian, Christopher Chandler, Safa Al-Sarraj, Lawrence J. Doey, Andrew J. Martin, Leslie Bridges, Matija Snuderl, David E. Kram, Uwe Kordes, Ulrich Schüller, Jeffrey Knipstein, Stephen Crosier, Mellissa Maybury, Catherine Rowe, Kathreena M. Kurian, Michael Hubank, Ji Wen, Wilda Orisme, James D. Dalton, Kelly Haupfear, Mark Kristiansen, Jane Chalker, Aimee Avery, Amy R. Fairchild, Alex Virasami, Louise Howell, Anna Burford, Valeria Molinari, Diana M. Carvalho, Sara Temelso, Elisa Izquierdo, Iris Stoler, Tejus A. Bale, Scott Newman, Ruth G. Tatevossian, Jessica C. Pickles, Britta Ismer, Alan Mackay, Matthew Clarke |
| Rok vydání: |
2023 |
| DOI: |
10.1158/2159-8290.c.6547883.v1 |
| Popis: |
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.Significance: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 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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