| Literature DB >> 32238360 |
Matthew Clarke1, Alan Mackay1, Britta Ismer2,3,4, Jessica C Pickles5, Ruth G Tatevossian6, Scott Newman7, Tejus A Bale8, Iris Stoler9, Elisa Izquierdo1, Sara Temelso1, Diana M Carvalho1, Valeria Molinari1, Anna Burford1, Louise Howell1, Alex Virasami5, Amy R Fairchild5, Aimee Avery5, Jane Chalker5, Mark Kristiansen5, Kelly Haupfear6, James D Dalton6, Wilda Orisme6, Ji Wen6, Michael Hubank10, Kathreena M Kurian11, Catherine Rowe11, Mellissa Maybury12,13,14, Stephen Crosier15, Jeffrey Knipstein16, Ulrich Schüller17,18, Uwe Kordes18, David E Kram19, Matija Snuderl20, Leslie Bridges21, Andrew J Martin22, Lawrence J Doey23, Safa Al-Sarraj23, Christopher Chandler24, Bassel Zebian24, Claire Cairns24, Rachael Natrajan25, Jessica K R Boult26, Simon P Robinson26, Martin Sill2, Ira J Dunkel27, Stephen W Gilheeney27, Marc K Rosenblum8, Debbie Hughes10, Paula Z Proszek10, Tobey J Macdonald28, Matthias Preusser29, Christine Haberler29,30, Irene Slavc31, Roger Packer32, Ho-Keung Ng33, Shani Caspi34, Mara Popović35, Barbara Faganel Kotnik36, Matthew D Wood37, Lissa Baird38, Monika Ashok Davare39, David A Solomon40,41, Thale Kristin Olsen42, Petter Brandal43, Michael Farrell44, Jane B Cryan44, Michael Capra45, Michael Karremann46, Jens Schittenhelm47, Martin U Schuhmann48, Martin Ebinger49, Winand N M Dinjens50, Kornelius Kerl51, Simone Hettmer52, Torsten Pietsch53, Felipe Andreiuolo53, Pablo Hernáiz Driever54, Andrey Korshunov55, Lotte Hiddingh2, Barbara C Worst2,4,56, Dominik Sturm2,4,56, Marc Zuckermann2,4, Olaf Witt2,4,56, Tabitha Bloom57, Clare Mitchell57, Evelina Miele58, Giovanna Stefania Colafati59, Francesca Diomedi-Camassei60, Simon Bailey15, Andrew S Moore12,13,14, Timothy E G Hassall13,61,62, Stephen P Lowis11, Maria Tsoli63,64, Mark J Cowley63,64, David S Ziegler63,64, Matthias A Karajannis27, Kristian Aquilina65, Darren R Hargrave66, Fernando Carceller67,68, Lynley V Marshall67,68, Andreas von Deimling55,69, Christof M Kramm70, Stefan M Pfister2,4,56, Felix Sahm54,69, Suzanne J Baker71, Angela Mastronuzzi72, Andrea Carai73, Maria Vinci58, David Capper9,74, Sergey Popov1,75, David W Ellison76, Thomas S Jacques77, David T W Jones78,4, Chris Jones79.
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. 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 commentary by Szulzewsky and Cimino, p. 904.This article is highlighted in the In This Issue feature, p. 890. ©2020 American Association for Cancer Research.Entities:
Year: 2020 PMID： 32238360 PMCID： PMC8313225 DOI： 10.1158/2159-8290.CD-19-1030
Source DB: PubMed Journal: Cancer Discov ISSN： 2159-8274 Impact factor: 39.397