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Alterations in ALK/ROS1/NTRK/MET drive a group of infantile hemispheric gliomas

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-12187-5

2041-1723

Ana Guerreiro Stücklin, Scott Ryall, Kohei Fukuoka, Michal Zápotocký, Álvaro Lassaletta, Christopher Li, Taylor Bridge, Byungjin Kim, Anthony Arnoldo, Paul E. Kowalski, Yunan Zhong, Monique Johnson, Claire Li, Arun Ramani, Robert Siddaway, Liana Nobre, Pasqualino de Antonellis, Christopher Dunham, Sylvia Cheng, Daniel R. Boué, Jonathan L. Finlay, Scott Coven, Inmaculada de Prada, Marta Pérez‐Somarriba, Cláudia C. Faria, Michael Grotzer, Elisabeth J. Rushing, David Sumerauer, Josef Zámečnı́k, Lenka Krsková, Miguel García-Ariza, Ofelia Cruz, Andrés Morales La Madrid, Palma Solano‐Páez, Keita Terashima, Yoshiko Nakano, Koichi Ichimura, Motoo Nagane, Hiroaki Sakamoto, Maria João Gil‐da‐Costa, Roberto Silva, Donna L. Johnston, Jean Michaud, Bev Wilson, Frank van Landeghem, Angélica Oviedo, P. Daniel McNeely, Bruce Crooks, Iris Fried, Nataliya Zhukova, Jordan R. Hansford, Amulya NageswaraRao, Livia Garzia, Mary Shago, Michael Brudno, Meredith S. Irwin, Ute Bartels, Vijay Ramaswamy, Éric Bouffet, Michael D. Taylor, Uri Tabori, Cynthia Hawkins,

MicroRNA in disease regulation

Infant gliomas have paradoxical clinical behavior compared to those in children and adults: low-grade tumors have a higher mortality rate, while high-grade tumors have a better outcome. However, we have little understanding of their biology and therefore cannot explain this behavior nor what constitutes optimal clinical management. Here we report a comprehensive genetic analysis of an international cohort of clinically annotated infant gliomas, revealing 3 clinical subgroups. Group 1 tumors arise in the cerebral hemispheres and harbor alterations in the receptor tyrosine kinases ALK, ROS1, NTRK and MET. These are typically single-events and confer an intermediate outcome. Groups 2 and 3 gliomas harbor RAS/MAPK pathway mutations and arise in the hemispheres and midline, respectively. Group 2 tumors have excellent long-term survival, while group 3 tumors progress rapidly and do not respond well to chemoradiation. We conclude that infant gliomas comprise 3 subgroups, justifying the need for specialized therapeutic strategies.