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.

World Health Organization (WHO) classifies brain tumors by their level of aggressiveness into four grades depending on their aggressiveness or malignancy as I to IV respectively [1]. From this classification of primary brain tumors, the four categories can be considered in two groups: Low Grade (LG) and High Grade (HG), in which the LG group is composed of grade I and II brain tumors, while the HG group is composed of grades III and IV brain tumors [2]. This paper focuses on the morphometric analysis of brain tumors and the study of the correlation of tumor shape with its degree of malignancy.