Journal Article

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

Arnoldo, Anthony, Johnson, Monique, Dunham, Christopher, Oviedo, Angelica, Nageswararao, Amulya, Wilson, Bev, de Prada, Inmaculada, Nagane, Motoo, Guerreiro Stucklin, Ana S., Faria, Claudia C., Fried, Iris, Bouffet, Eric, Cheng, Sylvia, Ramaswamy, Vijay, Finlay, Jonathan L., Perez-Somarriba, Marta, Bartels, Ute, Sumerauer, David, Hawkins, Cynthia, Brudno, Michael, Silva, Roberto, Michaud, Jean, Krskova, Lenka, McNeely, P. Daniel, Garzia, Livia, Hansford, Jordan R., Zapotocky, Michal, Ryall, Scott, Shago, Mary, Nobre, Liana Figueiredo, Solano, Palma, Taylor, Michael D., Coven, Scott L., Li, Claire, Grotzer, Michael A., Morales La Madrid, Andres, Terashima, Keita, Cruz, Ofelia, Tabori, Uri, Bridge, Taylor, van Landeghem, Frank K. H., Rushing, Elisabeth, Crooks, Bruce, Fukuoka, Kohei, Sakamoto, Hiroaki, Zamecnik, Josef, Zhukova, Nataliya, Kowalski, Paul E., Siddaway, Robert, Johnston, Donna L., Irwin, Meredith S., Zhong, Yvonne, Kim, Byungjin, Lassaletta, Alvaro, Li, Christopher, Boué, Daniel R., Nakano, Yoshiko, Gil-da-Costa, Maria Joao, Garcia Ariza, Miguel, Ichimura, Koichi, de Antonellis, Pasqualino, Ram

2019

Overview

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. Infant gliomas behave differently to their childhood or adult counterparts. Here, the authors perform a large-scale genetic analysis of these tumours, revealing genetic alterations which may offer therapeutic opportunities.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/106 / 13/44 / 13/51 / 14/32 / 38/22 / 45/23 / 45/77 / 45/91 / 631/67/69 / 64/60 / 692/4017 / Anaplastic Lymphoma Kinase - genetics / Anaplastic Lymphoma Kinase - metabolism / Brain Neoplasms - classification / Brain Neoplasms - genetics / Brain Neoplasms - metabolism / Cerebral hemispheres / Chemoradiotherapy / DNA Methylation / Epigenomics - methods / Female / Gene Expression Regulation, Neoplastic / Genetic analysis / Glioma / Glioma - classification / Glioma - genetics / Glioma - metabolism / Humanities and Social Sciences / Humans / Infant / Infant, Newborn / Infants / Kinases / Male / MAP kinase / multidisciplinary / Mutation / Protein-Tyrosine Kinases - genetics / Protein-Tyrosine Kinases - metabolism / Proto-Oncogene Proteins - genetics / Proto-Oncogene Proteins - metabolism / Proto-Oncogene Proteins c-met - genetics / Proto-Oncogene Proteins c-met - metabolism / Receptor Protein-Tyrosine Kinases - genetics / Receptor Protein-Tyrosine Kinases - metabolism / Receptor, trkA - genetics / Receptor, trkA - metabolism / Science / Science (multidisciplinary) / Subgroups / Survival / Survival Analysis / Tumors / Tyrosine / Whole Exome Sequencing - methods